共查询到20条相似文献,搜索用时 31 毫秒
1.
A screening of compound libraries based on nipecotic acid derivatives with lipophilic residues attached to the scarcely explored 5-position of the core structure was used for the search of new inhibitors of the γ-aminobutyric acid (GABA) transporter 1 (mGAT1). The generated compound libraries, which were based on hydrazone chemistry commonly used in dynamic combinatorial chemistry but rendered pseudostatic, were screened for their binding affinities toward mGAT1 by means of MS Binding Assays. With nipecotic acid derived hydrazone rac- 16 h [rac-(3R,5S)-{5-[(E)-2-{[5-(2-phenylethynyl)thiophen-2-yl]methylidene}hydrazin-1-yl]piperidine-3-carboxylic acid}-sodium chloride (1/2)], one hit was found and evaluated displaying sub-micromolar potency (pKi=6.62±0.04) and a noncompetitive interaction mode at mGAT1. By bearing a 5-(2-phenylethynyl)thiophen-2-yl residue attached to the 5-position of nipecotic acid via a three-atom spacer, compound rac- 16 h contains a structural moiety so far unprecedented for these kinds of bioactive molecules, and complements novel 5-substituted nipecotic acid derived ligands of mGAT1 revealed in a recently published screening campaign. This new class of ligands, with an inhibition mode distinct from that of benchmark mGAT1 inhibitors, could serve as research tools for investigations of mGAT1-mediated GABA transport. 相似文献
2.
Conjugated polymers were synthesized and used for polymer solar cells with new electron-rich units, 6-(2-thienyl)-4H-thieno[2,3-b]indole (2-TTI). 2-TTI was coupled with electron-pulling units, including benzothiadiazole and benzimidazole derivatives, to provide push–pull types of conjugated polymers (poly(8-(heptadecan-9-yl)-6-(thiophen-2-yl)-8H-thieno[2,3-b]indole)-alt-(2-methyl-5,6-bis(octyloxy)-4,7-di(thiophen-2-yl)-2-(trifluoromethyl)-2H-benzimidazole) (PTTIDOCF3), poly(8-(heptadecan-9-yl)-6-(thiophen-2-yl)-8H-thieno[2,3-b]indole)-alt-(5,6-bis(octyloxy)-4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole) (PTTIDOBT), poly(8-(heptadecan-9-yl)-6-(thiophen-2-yl)-8H-thieno[2,3-b]indole)-alt-(2,2-dimethyl-4,7-di(thiophen-2-yl)-2H-benzimidazole) (PTTIMBI), and poly(8-(heptadecan-9-yl)-6-(thiophen-2-yl)-8H-thieno[2,3-b]indole)-alt-(2,2-dimethyl-5,6-bis(octyloxy)-4,7-di(thiophen-2-yl)-2H-benzimidazole) (PTTIDOMBI)). The synthesized conjugated polymers provided deep highest occupied molecular orbital energy levels for higher open-circuit voltages (VOC). The device composed of PTTIDOMBI and [6,6]-Phenyl C71 butyric acid methyl ester PC71BM (1:2) with chloronaphthalene additive showed a VOC of 0.72 V, a short-circuit current (JSC) of 9.16 mA/cm2, and a fill factor of 0.43; this gave a power conversion efficiency (PCE) of 2.84%. The PTTIDOMBI provided better morphology for enhanced charge transport, and this led to the higher JSC and PCE of the organic solar cells. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47624. 相似文献
3.
A new class of nipecotic acid and guvacine derivatives has been synthesized and characterized for their inhibitory potency at mGAT1–4 and binding affinity for mGAT1. Compounds of the described class are defined by a four-carbon-atom allenyl spacer connecting the nitrogen atom of the nipecotic acid or guvacine head with an aromatic residue. Among the compounds investigated, the mixture of nipecotic acid derivatives rac-{(Ra)-1-[4-([1,1′:2′,1′′-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} and rac-{(Sa)-1-[4-([1,1′:2′,1′′-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} ( 21 p ), possessing an o-terphenyl residue, was identified as highly selective and the most potent mGAT1 inhibitor in this study. For the (R)-nipecotic acid derived form of 21 p , the inhibitory potency in [3H]GABA uptake assays was determined as pIC50=6.78±0.08, and the binding affinity in MS Binding Assays as pKi=7.10±0.12. The synthesis of the designed compounds was carried out by a two-step procedure, generating the allene moiety via allenylation of terminal alkynes which allows broad variation of the terminal phenyl and biphenyl subunit. 相似文献
4.
Jia-Cheng Shen Rong-Zhang Jin Kai Yuan Mei-Mei Zhang 《Polycyclic Aromatic Compounds》2016,36(5):758-772
A three-component reaction of benzaldehyde, 5,5-dimethyl-3-(arylamino)cyclohex-2-enone and 4-hydroxyquinolin-2(1H)-one gave a series of 3-((4,4-dimethyl-6-oxo-2-(arylamino) cyclohex-1-en-1-yl)(aryl)methyl)-4-hydroxyquinolin-2(1H)-one derivatives in ionic liquids at 80°C under catalyst-free conditions. In the presence of TsOH at 140°C, the same reaction provided an efficient method for the synthesis of 7-aryl-10,10-dimethyl-10,11-dihydro-5H-chromeno[3,2-c] quinoline-6,8(7H,9H)-dione derivatives in high yields while aromatic amine losing unexpectedly. 相似文献
5.
Fang Yan Guo Prof. Chang Ji Zheng Meiyuan Wang Jiangping Ai Lan Ying Han Liu Yang Ye Fang Lu Yu Xuan Yang Prof. Ming Guan Piao Prof. Hu-Ri Piao Prof. Chun-Mei Jin Prof. Cheng Hua Jin 《ChemMedChem》2021,16(15):2354-2365
Three series of new imidazole-fused imidazo[2,1-b][1,3,4]thiadiazole analogues (compounds 20 a – g , 21 a – g , and 22 a – g ) have been synthesized, and their antibacterial and antifungal activities have been evaluated. All the target compounds showed strong antifungal activity and high selectivity for the test fungus Candida albicans over Gram-positive and -negative bacteria. N-((4-(2-Cyclopropyl-6-(4-fluorophenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)-5-(6-methyl-pyridin-2-yl)-1H-imidazol-2-yl)methyl)aniline ( 21 a ) showed the highest activity against C. albicans (MIC50=0.16 μg/mL), 13 and three times that of the positive control compounds gatifloxacin and fluconazole, respectively. Compounds 21 a and 20 e did not show cytotoxicity against human foreskin fibroblast-1 cells, and compound 21 a was as safe as the positive control compounds in hemolysis tests. These results strongly suggest that some of the compounds produced in this work have value for development as antifungal agents. 相似文献
6.
Dr. Benedikt Martin Dr. Dirk Schepmann Dr. Freddy A. Bernal Prof. Thomas J. Schmidt Prof. Tao Che Prof. Karin Loser Prof. Bernhard Wünsch 《ChemMedChem》2020,15(15):1408-1420
Racemic K-opioid receptor (KOR) agonist 2-(3,4-dichlorophenyl)-1-[(4aRS,8SR,8aSR)-8-(pyrrolidin-1-yl)-3,4,4a,5,6,7,8,8a-octahydroquinolin-1(2H)-yl]ethan-1-one ((±)- 4 ) was prepared in a diastereoselective synthesis. The first key step of the synthesis was the diastereoselective hydrogenation of the silyl ether of 1,2,3,4-tetrahydroquinoin-8-ol ((±)- 9 ) to afford cis,cis-configured perhydroquinoline derivative (±)- 10 . Removal of the TBDMS protecting group led to a β-aminoalcohol that reacted with SO2Cl2 to form an oxathiazolidine. Nucleophilic substitution with pyrrolidine resulted in the desired cis,trans-configured perhydroquinoline upon inversion of the configuration. In order to obtain enantiomerically pure KOR agonists 4 (99.8 % ee) and ent- 4 (99.0 % ee), 1,2,3,4-tetrahydroquinolin-8-ols (R)- 8 (99.1 % ee) and (S)- 8 (98.4 % ee) were resolved by an enantioselective acetylation catalyzed by Amano lipase PS-IM. The absolute configuration was determined by CD spectroscopy. The 4aR,8S,8aS-configured enantiomer 4 showed sub-nanomolar KOR affinity (Ki=0.81 nM), which is more than 200 times higher than the KOR affinity of its enantiomer ent- 4 . In the cAMP assay and the Tango β-arrestin-2 recruitment assay, 4 behaved as a KOR agonist. Upon incubation of human macrophages, human dendritic cells, and mouse myeloid immune cells with 4 , the number of cells expressing co-stimulatory receptor CD86 and proinflammatory cytokines interleukin 6 and tumor necrosis factor α was significantly reduced; this indicates the strong anti-inflammatory activity of 4 . The anti-inflammatory effects correlated well with the KOR affinity: (4aR,8S,8aS)- 4 was slightly more potent than the racemic mixture (±)- 4 , and the distomer ent- 4 was almost inactive. 相似文献
7.
J. Heinicke Th. Ristau S. Jelonek M. Mühlstdt 《Advanced Synthesis \u0026amp; Catalysis》1996,338(1):327-336
Bis-(1-chloro-3-phenoxy-prop-2-yl)-sulfanes – Nucleophilic Displacement and Regiochemistry. Separation and Assignment of Diastereomers. Synthesis of Diastereomerically Pure Trithiacycles The title compounds 1 were substituted by a series of O-, N- and S-nucleophiles (H2O solvolysis, AgOAc, NaN3, KSCN, NaSPh, thiourea). A strong tendency to β-elimination of HCl depending on the kind of the attacking nucleophile was found. In most cases no regioisomerization could be detected in the isolated products of the nucleophilic displacement. Best results were obtained with sulfur nucleophiles. The separation of the diastereomeric mixture of the p-kresyl derivative 1b into the individual diastereomers 1bA and 1bB in a preparative scale was achieved. These 3-thia-1,5-dichlorides and several products of substitution could be assigned to the meso- or (±)-form by examination of the stereochemistry and symmetry of the corresponding sulfoxides. The 1,5-dimercapto derivatives 8 are convenient as structural units for the synthesis of diastereomerically pure cis- or trans-disubstituted trithiacycles e.g. 15bA , 15bB . The (±)-form of the 4,6-disubstituted 2,5,8-trithia[9]-(2,6)-pyridinophane 16bA was characterized by X-ray crystal structure determination. 相似文献
8.
This paper describes an investigation into the suitability – for the determination of enthalpies of sublimation of low volatility substances – of thermal conductivity manometers which are operated according to the method described by Engelsman. By making use of the known vapour pressure-temperature relation of liquid mercury the characteristics of the manometers are obtained. They show deviations from linearity at higher pressures; in spite of this the most suitable manometers still have linear ranges of three to four decades. One of the thermal conductivity manometers (TCM) was used for the determination of the enthalpies of sublimation of benzophenone (ΔsH = 22.60 ± 0.10 kcal mole−1), benzoic acid (ΔsH = 21.05 ± 0.05 kcal mole−1), ferrocene (ΔsH = 17.7 ± 0.4 kcal mole−1) and trans-stilbene (ΔsH = 24.40 ± 0.15 kcal mole−1). As the measurements on ferrocene fell outside the linear range of the manometer, it was necessary to introduce a correction coefficient derived from the measurements on benzophenone and benzoic acid in order to obtain satisfactory results. 相似文献
9.
《分离科学与技术》2012,47(3):480-486
The extraction of uranium (VI) from 5.3 mol.L?1 phosphoric acid with a series of phosphoric, phosphinic, dithiophosphoric, or dithiophosphinic acid derivatives (0.5 mol.L?1) in mixture with 0.125 mol.L?1 TOPO in Isane IP 185 has been investigated. In the frame of the present work, eight acidic phosphorus and thiophosphorus compounds have been synthesized: bis(1,3-diisobutoxypropan-2-yl) phosphoric acid, bis(1,3-bis-(butylthio)propan-2-yl) phosphoric acid, bis(5,8,12,15-tetraoxanonadecan-10-yl) phosphoric acid, bis(1-butoxyheptan-2-yl) phosphoric acid, bis(undecan-6-yl) phosphoric acid, bis(2-(1,3-dibutoxypropan-2-yloxy)ethyl) phosphoric acid, bis(3-butoxy-2-(butoxymethyl)-2-methylpropyl) phosphinic acid, bis(1,3-dibutoxypropan-2-yl) dithiophosphoric acid. The properties of these molecules in mixtures with TOPO have been compared with those of other extractants such as bis(2-ethylhexyl) phosphoric acid, bis(2-ethylhexyl) dithiophosphoric acid, bis(2-ethylhexyl) phosphinic acid, Cyanex® 272, and Cyanex® 301. The replacement of phosphoric acid-type extractant by their phosphinic homologues dramatically decreases the affinity for uranium (VI) whereas the replacement of the phosphoric and phosphinic acid-type extractants by their dithio homologues affects positively the distribution coefficient of uranium (VI). It also appears that the steric hindrance effect is responsible for a significant decrease of the distribution coefficient of uranium (VI). Supplemental materials are available for this article. Go to the publisher's online edition of Separation Science and Technology to view the free supplemental file. 相似文献
10.
《Applied Clay Science》2004,25(3-4):221-227
Polymer–clay composites of poly([2-(methacryloxy)ethyl]trimethylammonium chloride) and various clayey minerals have been prepared by visible light-induced free radical polymerization. The starting monomer–clay formulation contained: (i) the initiating dye, Rose bengal derivative, (2′[6-(3-trimethylaminopropoxy)-2,4-diiodo-3-oxo-3H-xanthen-9-yl]-benzyloxy-propyltrimethyl-ammonium dibromide, DBEE); (ii) the electron donor, 2-(dimethyl-amino)ethyl methacrylate; and (iii) the crosslinking monomer, poly(ethylene glycol) dimethacrylate. The method allows to prepare 1–2 mm thick foils that can be formed under both artificial lights and the sunlight exposition. The foil is flexible and insoluble in water. The clay is not rinsed out from the composite even after hundreds of hours of water treatment. The obtained composites do not exhibit good mechanical properties. 相似文献
11.
Chung Sub Kim Won Se Suh Lalita Subedi Sun Yeou Kim Sang Un Choi Kang Ro Lee 《Lipids》2016,51(8):989-995
Phytochemical investigation of the bark from the stems of Sorbus commixta led to the isolation and characterization of a new fatty acid, sorcomic acid ( 1 ), along with nine known analogues ( 2 – 10 ). The structure of the new compound ( 1 ) was determined through NMR (1H and 13C NMR, HSQC, HMBC, and NOESY), MS, and specific optical rotation. The known compounds ( 2 – 10 ) were identified by comparison of their spectroscopic data with those in the literature. The biological activities of all the isolated compounds ( 1 – 10 ) were evaluated: compounds 1 , 5 , and 7 potently induced NGF secretion from C6 glioma cells (233.40 ± 12.82, 194.40 ± 8.05, and 185.74 ± 10.25 %, respectively) and compound 10 reduced NO levels with an IC50 value of 71.25 μM in murine microglia BV2 cells stimulated by LPS. 相似文献
12.
Jolita Ostrauskaite Vygintas Jankauskas Juozas V. Grazulevicius 《Polymer Bulletin》2002,49(2-3):95-101
Summary
The oligomer containing 9-[2-(9H-carbazo1-9-yl)cyclobutyl]-9H-carbazole moiety in the main chain and its model compound were synthesized by Wittig reaction. Both compounds form glasses
with glass transition temperatures of 254°C and 135°C respectively. The optical and photoelectrical properlies of the compounds
were studied. The hole drift mobilities observed in the film of the oligoiner by the time of flight technique were in the
range of 2·10−6 – 7·10−6 cm2/(V·s) at an applied electric field ranging from 5·8.104 to 2·7.105 V/cm.
Rcceivcd: 3 April 2002/Revised version: 16 July 2002/ Accepted: 5 August 2002
Correspondence to Juozas V. Grazulevicius e-mail: juogra@ctf.ktu.lt. Tel/Fax: +37 07 456525 相似文献
13.
Several substituted diglycolamides, namely TPDGA, THDGA, TODGA, and TDDGA, were evaluated in a comparative study on the extraction of hexavalent actinide ions such as UO22+, NpO22+, and PuO22+ from nitric acid medium. The acid extraction constants (KH) for the diglycolamides were determined to be 3.8 ± 0.6, 1.6 ± 0.1, 4.1 ± 0.4, and 1.4 ± 0.2 for TPDGA, THDGA, TODGA, and TDDGA, respectively. Though metal ion extraction generally increased with increasing the feed acid concentration, the nature of the extracted species changed with aqueous-phase acidity. While complexes of the type MO2(NO3)2·nL (where L is the diglycolamide extractant and n is 1 and 2) were found to be extracted at 1 M HNO3, the average number of ligand molecules associated with the complex decreased to ?1 when the nitric acid concentration increased to 3 M. These results have great significance from the actinide separation point of view, as the actinides ions can be made virtually inextractable by adjusting their oxidation state. The thermodynamic parameters were also calculated, which indicated spontaneous reactions with large exothermicities. 相似文献
14.
Justyna Popi Agnieszka Gunia-Krzyak Karolina Soczyska Paulina Koczurkiewicz-Adamczyk Kamil Piska Katarzyna Wjcik-Pszczoa Dorota elaszczyk Anna Krupa Pawe mudzki Henryk Marona Elbieta Pkala 《International journal of molecular sciences》2021,22(1)
Excessive UV exposure contributes to several pathological conditions like skin burns, erythema, premature skin aging, photodermatoses, immunosuppression, and skin carcinogenesis. Effective protection from UV radiation may be achieved with the use of sunscreens containing UV filters. Currently used UV filters are characterized by some limitations including systemic absorption, endocrine disruption, skin allergy induction, and cytotoxicity. In the research centers all over the world new molecules are developed to improve the safety, photostability, solubility, and absorption profile of new derivatives. In our study, we designed and synthesized seventeen novel molecules by combining in the structures two chromophores: xanthone and (E)-cinnamoyl moiety. The ultraviolet spectroscopic properties of the tested compounds were confirmed in chloroform solutions. They acted as UVB or UVA/UVB absorbers. The most promising compound 9 (6-methoxy-9-oxo-9H-xanthen-2-yl)methyl (E)-3-(2,4-dimethoxyphenyl)acrylate) absorbed UV radiation in the range 290–369 nm. Its photoprotective activity and functional photostability were further evaluated after wet milling and incorporation in the cream base. This tested formulation with compound 9 possessed very beneficial UV protection parameters (SPFin vitro of 19.69 ± 0.46 and UVA PF of 12.64 ± 0.32) which were similar as broad-spectrum UV filter tris-biphenyl triazine. Additionally, compound 9 was characterized by high values of critical wavelength (381 nm) and UVA/UVB ratio (0.830) thus it was a good candidate for broad-spectrum UV filter and it might protect skin against UVA-induced photoaging. Compound 9 were also shown to be photostable, non-cytotoxic at concentrations up to 50 µM when tested on five cell lines, and non-mutagenic in Ames test. It also possessed no estrogenic activity, according to the results of MCF-7 breast cancer model. Additionally, its favorable lipophilicity (miLogP = 5.62) does not predispose it to penetrate across the skin after topical application. 相似文献
15.
Shadpour Mallakpour Mohammad Dinari 《Polymer-Plastics Technology and Engineering》2015,54(14):1439-1447
Hybrid of acid functionalized multiwalled carbon nanotubes and layered double hydroxides were prepared by coprecipitation reaction of the Al(NO3)3·9H2O, Mg(NO3)2·6H2O, and acid functionalized multiwalled carbon nanotubes under ultrasonic irradiation. An optically active amino acid containing poly(amide-imide) was synthesized by the direct polycondensation reaction of the N,N′-(pyromellitoyl)-bis-L-isoleucine diacid and diamine using molten tetra-n-butylammonium bromide. These three-dimensional nanofillers were used as reinforcing agent to enhance the performance of chiral poly(amide-imide). The structure and morphology of the hybrid materials were confirmed by Fourier transformed infrared spectroscopy, X-ray diffraction, field emission and transmission electron microscopy, and thermogravimetry analysis techniques. 相似文献
16.
Identification of the California red scale sex pheromone 总被引:2,自引:0,他引:2
W. Roelofs M. Gieselmann A. Cardé H. Tashiro D. S. Moreno C. A. Henrick R. J. Anderson 《Journal of chemical ecology》1978,4(2):211-224
Pheromone components of female California red scale,Aonidiella aurantii (Maskell) were isolated from airborne collections and found to be 3-methyl-6-isopropenyl-9-decen-1-yl acetate and (Z)-3-methyl-6-isopropenyl-3,9-decadien-1-yl acetate. Both enantiomers of the latter compound as well as the corresponding enantiomers of theE isomer were prepared from (S)- or (R)-carvone. Bioassays with each of the four isomers showed that only theR,Z isomer attracted male red scale.
Aonidiella aurantii (Maskell) (Homoptera: Diaspididae).This research was supported by a USDA Cooperative Research Grant. 相似文献
17.
To date, most studies of the thermodynamic properties of organic aerosols have utilized test aerosols generated by spray atomization followed by a diffusion drying step. Some evidence points to possible biases in measured thermodynamic properties stemming from the presence of residual solvent (water or alcohol) in the dried aerosol. In the current study we compared measurements of thermodynamic properties of organic aerosols generated by atomization of aqueous solutions to those generated by homogeneous condensation using a modified Sinclair-La Mer generator. In particular, using the Integrated Volume Method (Saleh et al. 2008), we measured and compared the saturation pressure (P sat ) at 298 K and enthalpy of vaporization (ΔH) of C-6 (adipic) and C-9 (azelaic) dicarboxylic acid aerosol generated using these techniques. We found that P sat and ΔH exhibited no statistically significant difference across the tested aerosol generation methods, indicating that any residual solvent carried by the particles had no impact on the measurements. For adipic acid, we obtained P sat of 3.3 × 10?5 (±0.9 × 10?5) Pa and ΔH of 132 (±8) kJ/mol with atomization, and P sat of 4.2 × 10? 5 (±2.2 × 10?5) Pa and ΔH of 126 (±21) kJ/mol with homogeneous condensation; for azelaic acid, we obtained P sat of 1.4 × 10?5 (±0.5 × 10?5) Pa and ΔH of 145 (±15) kJ/mol with atomization, and P sat of 0.9 × 10? 5 (±0.3 × 10? 5) Pa and ΔH of 158 (±17) kJ/mol with homogeneous condensation. In addition, SEM images of the acids generated by the two methods showed no obvious difference in surface morphology. 相似文献
18.
The anodic behavior of the cardiotonic drug 3-amino-5-(pyrid-4-yl)-1,2-dihydropyrid-2-one 1 and of 6 compounds with similar structure was investigated at platinum and vitreous carbon electrodes in acetonitrile and in aqueous medium. Caused by the 3-amino group 1 is oxidized at a relatively small oxidation potential in an irreversible two-electron process. Depending on the addition of a strong base or a strong acid the oxidation potential vs. SCE in acetonitrile is −0.08 V (anion), +0.66 V (neutral compound), +0.93 V (monocation) or +1.15 V (dication). In H2O a strong decrease of the oxidation potential with increasing pH was found as a reason for the sensitivity of 1 against oxygen in alkaline solution. The anodic oxidation of 3-dimethylamino-5-(pyrid-4-yl)-1, 2-dihydro-pyrid-2-one 3 in 0.1 m H2SO4 leads to 5-(pyrid-4-yl)-piperidine-2,3,6-trione 9a or 5-(pyrid-4-yl)-piperidine-2,3,4-trione 9b , which is also the oxidation product of 1 at small concentration. At high concentration of 1 coupling reactions at the 3-amino-group lead to dimeric products, which could not be identified. 相似文献
19.
Enzymatically Modified Shea Butter and Palm Kernel Oil as Potential Lipid Drug Delivery Matrices
下载免费PDF全文
![点击此处可从《European Journal of Lipid Science and Technology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nicholas C. Obitte Katja Zorn Isabel Oroz‐Guinea Uwe T. Bornscheuer Sandra Klein 《European Journal of Lipid Science and Technology》2018,120(4)
20.
Single Heteroatom Substitutions in the Efavirenz Oxazinone Ring Impact Metabolism by CYP2B6
下载免费PDF全文
![点击此处可从《ChemMedChem》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Previously, we observed that the oxazinone ring is important for cytochrome P450 2B6 (CYP2B6) activity toward efavirenz ((4S)‐6‐chloro‐4‐(2‐cyclopropylethynyl)‐1,4‐dihydro‐4‐(trifluoromethyl)‐2H‐3,1‐benzoxazin‐2‐one), a CYP2B6 substrate used to treat HIV. To further understand the structural characteristics of efavirenz that render it a CYP2B6 substrate, we tested the importance of each heteroatom of the oxazinone ring. We assembled a panel of five analogues: 6‐chloro‐4‐(2‐cyclopropylethynyl)‐1,4‐dihydro‐2‐methyl‐4‐(trifluoromethyl)‐2H‐3,1‐benzoxazine ( 1 ), (4S)‐6‐chloro‐4‐[(1E)‐2‐cyclopropylethenyl]‐3,4‐dihydro‐4‐(trifluoromethyl)‐2(1H)‐quinazolinone ( 2 ), (4S)‐6‐chloro‐4‐(2‐cyclopropylethynyl)‐3,4‐dihydro‐4‐(trifluoromethyl)‐2(1H)‐quinazolinone ( 3 ), 6‐chloro‐4‐(cyclopropylethynyl)‐3,4‐dihydro‐4‐(trifluoromethyl)‐2(1H)‐quinolinone ( 4 ), and 6‐chloro‐4‐(cyclopropylethynyl)‐4‐(trifluoromethyl)‐4H‐benzo[d][1,3]dioxin‐2‐one ( 5 ). The metabolism of compounds 1 – 5 was investigated using human liver microsomes, individual P450s, and mass spectrometry or UV/Vis absorbance detection. Steady‐state analysis of CYP2B6 metabolism of 1 – 5 showed KM values ranging from 0.3‐ to 3.9‐fold different from that observed for efavirenz (KM: 3.6±1.7 μm ). The lowest KM values, approximating 1 μm , were observed for the metabolism of 1 , whereas the greatest KM value, 14±6.4 μm , was found for 4 . Our work reveals that analogues with heteroatom changes in the oxazinone ring are still CYP2B6 substrates, although the changes in KM suggest altered substrate binding. 相似文献