- Direct Synthesis of γ-Substituted Phthalides Via ortho-Aryl Benzoic Acid Mediated Benzyl Radical Cyclization
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Direct synthesis of γ-substituted phthalids from related ortho-aryl benzoic acids with 48-85% yield are covered. The direct oxidation in the presence of peroxydisulphate-copper (II) chloride in aqueous medium was applied. The reaction is highly regioselective and leads exclusively to γ-butyrolactone, through very stable benzylic radical intermediate.
- Mahmoodi,Salehpour
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- Synthesis of biaryl imino/keto carboxylic acids via aryl amide directed C-H activation reaction
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A novel Pd-catalysed C-H activation reaction for the synthesis of biaryl imino/keto carboxylic acids is developed. This reaction underwent aryl amide directed C-H activation ortho-acylation followed by ring closing and ring opening processes to give a range of biaryl imino/keto carboxylic acids. Our methodology features the utilization of a cheap and green oxidant (TBHP) as well as readily available aldehydes.
- Zhang, Nana,Yu, Qingzhen,Chen, Ruixue,Huang, Jianhui,Xia, Yeqing,Zhao, Kang
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- Direct synthesis of γ-substituted phthalides by cyclization of benzyl radicals generated from o-(arylmethyl)benzoic acids
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Direct oxidation of o-(arylmethyl)benzoic acids with sodium peroxysulfate-copper(II) chloride in water yields γ-substituted phthalides. The reaction is highly regioselective, and the corresponding γ-butyro-lactones are the only products formed through intermediate stable arylmethyl radicals.
- Mahmoodi,Salehpour
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- A Novel Three-Step Tandem Reaction for Efficient Syntheses of Bulky Anthracenyl Esters from 2-Benzylbenzoic Acids
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Bulky anthracenyl esters could be efficiently synthesized from 2-benzylbenzoic acids via a novel three-step tandem reaction containing intramolecular Friedel-Crafts acylation, enolization, and esterification. A mechanism for the tandem reaction is proposed.
- Wang, Yabai,Yang, Shiwei,Bian, Guangling,Song, Ling
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- The reaction of arylcoppermagnesium and other organometallic reagents with phthalic anhydride
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Arylcoppermagnesium reagents, prepared from 5ArMgX + 2.5CuI, (Ar = 4-CH3C6H4, 4-CH3OC6H4, 4-ClC6H4, 2-C4H3S) react with one equivalent of phthalic anhydride in ether or THF at -5 deg C for 2.5 h to give 2-aroylbenzoic acid in 83-98percent yields.The phenylcoppermagnesium reagent (Ar = C6H5) under similar conditions gives 2-benzoylbenzoic acid and 3,3-diphenylphthalide in 40-42percent and 42-45percent yield, respectively.The yield of the 2-benzoylbenzoic acid rises to 93percent in the presence of dimethyl sulphide.Under these conditions no phthalide is formed.Lithium diphenylcuprate reactswith phthalic anhydride in ether-hexane to give 92percent of 2-benzoylbenzoic acid and 7percent of 3,3-diphenylphthalide.The reaction of phenylcopper reagent, prepared from PhMgBr + CuI, under similar conditions is slow and gives 2-benzoylbenzoic acid in 15percent yield.The reaction of phenylmagnesium bromide in the presence or absence of catalytic amounts of copper(I) iodide gives unsatisfactory results.Use of two equivalents of phenyllithium with one equivalent of phthalic anhydride, on the other hand, affords 3,3-diphenylphthalide in 77percent yield.The mechanisms of these reactions are discussed.
- Rahman, Mohammed T.,Nahar, Syeda K.
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- Completing the Redox-Series of Silicon Trisdioxolene: ortho-Quinone and Lewis Superacid Make a Powerful Redox Catalyst
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Quinones are mild oxidants, the redox potentials of which can be increased by supramolecular interactions. Whereas this goal has been achieved by hydrogen bonding or molecular encapsulation, a Lewis acid-binding strategy for redox amplification of quinones is unexplored. Herein, the redox chemistry of silicon tris(perchloro)dioxolene 1 was studied, which is the formal adduct of ortho-perchloroquinone QCl with the Lewis superacid bis(perchlorocatecholato)silane 2. By isolating the anionic monoradical 1.?, the redox-series of a century-old class of compounds was completed. Cyclic voltammetry measurements revealed that the redox potential in 1 was shifted by more than 1 V into the anodic direction compared to QCl, reaching that of “magic blue” or NO+. It allowed oxidation of challenging substrates such as aromatic hydrocarbons and could be applied as an efficient redox catalyst. Remarkably, this powerful reagent formed in situ by combining the two commercially available precursors SiI4 and QCl.
- Maskey, Rezisha,Bendel, Christoph,Malzacher, Jonas,Greb, Lutz
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- Construction of an isoquinolinone framework from carboxylic-ester-directed umpolung ring opening of methylenecyclopropanes
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An interesting type of reaction involving functionalized methylenecyclopropanes (MCPs) has been revealed. Here, a nucleophilic attack of an anionic species onto a partially polarity-reversed MCP was realized by treating a neighbouring carboxylic ester tethered to the MCP and amine with KHMDS to realize an umpolung ring opening of the MCP. This work established an operationally convenient protocol for the rapid construction of isoquinolinone frameworks. This journal is
- Wei, Hao-Zhao,Wei, Yin,Shi, Min
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supporting information
p. 11201 - 11204
(2021/11/09)
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- A facile greener synthesis, antimicrobial evaluation and molecular modelling of new 4-aryl-2-(3-(2-(trifluoromethyl)phenyl)-1,8-naphthyridin-2-yl)phthalazin-1(2H)-one derivatives
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Abstract: The synthesis of 4-aryl-2-(3-(2-(trifluoromethyl)phenyl)-1,8-naphthyridin-2-yl)phthalazin-1(2H)-ones was performed by cyclization of 2-hydrazinyl-3-(2-(trifluoromethyl)phenyl)-1,8-naphthyridine with 2-aroylbenzoic acids in ethanol containing a catalytic amount of concentrated sulfuric acid under solid state conditions. All these synthesized compounds (8a–h) were screened for their in vitro antibacterial activity against gram-positive bacteria such as (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli) and also evaluated for their antifungal activity against Aspergillus Niger and Helmenthosphorium oryzae fungal strains. Some of the products demonstrate good antibacterial activity and moderate antifungal activity. In predominantly, 8b, 8d, 8g, and 8h compounds showed good to excellent antibacterial and antifungal activities. The antimicrobial activity of the compound 8 was further investigated with the help of in LibDock score docking study to predict the active sites. Graphical abstract: [Figure not available: see fulltext.].
- Sakram, Boda,Ravi, Dharavath,Raghupathi, Mutyala,Kumar, Boda Sathish,Anantha Lakshmi
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p. 2007 - 2022
(2019/01/10)
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- Metal-Free Arylation-Lactonization Sequence of γ-Alkenoic Acids Using Anilines as Aryl Radical Precursors
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The presence of salicylic acid (10 mol-%) and H2O (10 equiv.) significantly improves the arylation-lactonization sequence of γ-alkenoic acids with in situ formed diazonium salts (from bench stable anilines). The reaction is finished in less than 5 h without thermal or photochemical activation, giving access to a variety of γ,γ-disubstituted butyrolactones. The protocol is user-friendly and can be used at gram-scale or adapted to transform alkenols into phthalanes. Control experiments revealed that aryl radicals participate in the reaction and a plausible mechanism is proposed to include this and other mechanistic investigations, for the catalyzed and the background reaction.
- Felipe-Blanco, Diego,Gonzalez-Gomez, Jose C.
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supporting information
p. 7735 - 7744
(2019/12/24)
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- Preparation method and epoxidation application of phthalazinone bisphenol monomer
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The invention belongs to the technical field of new materials, and discloses a preparation method and epoxidation application of a phthalazinone bisphenol monomer. The method comprises the following steps: (1) preparing MHPZ by a Friedel-Crafts reaction; (2) synthesizing an MMPZ monomer by using the MHPZ, 4-bromoanisole (BPM), 1,10-phenanthroline (PNTM) and CuI by a "one-pot two-step method"; and(3) reducing the MMPZ by Lewis acid to obtain the target monomer HHPZ. The synthesis method has the advantages of mild reaction condition, simple and convenient product post-treatment and high productpurity. Through detection by liquid chromatography-mass spectrometry, the purity of the target monomer is 99% and the yield is 90% or above. Based on the above synthetic exploration, two ends of thesynthesized active bisphenol monomer were further functionalized. Active hydroxyl groups at two ends of HHPZ are epoxidized with epichlorohydrin, and then novel intrinsic flame retardant epoxy resin with a low melting point and high temperature resistance is achieved, wherein the flame retardant grade can reach the V-0 grade.
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Paragraph 0025-0026
(2019/11/21)
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- Ruthenium-Catalyzed Enantioselective Hydrogenation/Lactonization of 2-Acylarylcarboxylates: Direct Access to Chiral 3-Substituted Phthalides
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Highly enantioselective tandem hydrogenation/lactonization of various 2-acylarylcarboxylates including 2-aroylarylcarboxylates were realized by using [RuCl(benzene)(S)-SunPhos]Cl as the catalyst under mild reaction conditions. Excellent enantioselectivities (up to 99.6 % ee) and activities (S/C=1000) were obtained. This convenient and practical method enables a direct access to a series of highly optically pure 3-substituted phthalides that are very important molecules as valuable pharmacological compounds and diversified synthons for medicinal chemistry. Moreover, a gram-scale reaction was performed to further demonstrate the practicality of this approach.
- Lu, Bin,Zhao, Mengmeng,Ding, Guangni,Xie, Xiaomin,Jiang, Lili,Ratovelomanana-Vidal, Virginie,Zhang, Zhaoguo
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p. 3989 - 3996
(2017/09/13)
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- Preparation method of 2-(4-hydroxybenzoyl)benzoic acid
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The invention belongs to the technical fields of fine chemical engineering and preparation of drug intermediates, and particularly relates to a preparation method of 2-(4-hydroxybenzoyl)benzoic acid. The preparation method comprises the following steps: heating and refluxing anisole and phthalic anhydride under the action of a Lewis acid catalyst to conduct a friedel-crafts acylation reaction to obtain an intermediate 2-(4-methoxybenzoyl) benzoic acid, then heating and refluxing under the action of a hydrobromic acid solution to sufficiently react to prepare the 2-(4-hydroxybenzoyl)benzoic acid of the target product. Compared with the prior art, the prepared 2-(4-hydroxybenzoyl)benzoic acid is good in quality and higher in yield, and the preparation method is simple in preparation process, mild in conditions, low in energy consumption, low in cost and suitable for mass production.
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Paragraph 0027; 0031; 0035
(2017/07/20)
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- Activation of Electron-Deficient Quinones through Hydrogen-Bond-Donor-Coupled Electron Transfer
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Quinones are important organic oxidants in a variety of synthetic and biological contexts, and they are susceptible to activation towards electron transfer through hydrogen bonding. Whereas this effect of hydrogen bond donors (HBDs) has been observed for Lewis basic, weakly oxidizing quinones, comparable activation is not readily achieved when more reactive and synthetically useful electron-deficient quinones are used. We have successfully employed HBD-coupled electron transfer as a strategy to activate electron-deficient quinones. A systematic investigation of HBDs has led to the discovery that certain dicationic HBDs have an exceptionally large effect on the rate and thermodynamics of electron transfer. We further demonstrate that these HBDs can be used as catalysts in a quinone-mediated model synthetic transformation.
- Turek, Amanda K.,Hardee, David J.,Ullman, Andrew M.,Nocera, Daniel G.,Jacobsen, Eric N.
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supporting information
p. 539 - 544
(2016/02/27)
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- Synthesis and biological evaluation of 4-arylphthalazones bearing benzenesulfonamide as anti-inflammatory and anti-cancer agents
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Nine 4-arylphthalazones bearing benzenesulfonamide (2a-i) were synthesized by the condensation of the appropriate 2-aroylbenzoic acid (1a-i) and 4-hydrazinobenzenesulfonamide in ethanol. The structures of these compounds were elucidated by elemental analysis, IR, 1H NMR, 13C NMR, and MS spectroscopy. Two compounds, 2b and 2i, showed significant anti-inflammatory activity comparable to that of the standard drug celecoxib in the carrageenan-induced rat paw edema model. These compounds (2b and 2i) had selective inhibitory activity towards the COX-2 enzyme. Compound 2b had a better selectivity ratio (COX-1/COX-2) compared to that of celecoxib and can be used as a novel template for the design of selective COX-2 inhibitors. Compounds 2d and 2i were screened for their antiproliferative activity toward 60 human cancer cell lines by the National Cancer Institute (USA). The compounds 2d and 2i displayed mild activity toward the renal cancer cell line UO-31. Nine 4-arylphthalazones bearing benzenesulfonamide (2a-i) were synthesized by the condensation of the appropriate 2-aroylbenzoic acid (1a-i) and 4-hydrazinobenzenesulfonamide in ethanol. Compounds 2b and 2i showed anti-inflammatory activity comparable to that of celecoxib in the carrageenan-induced rat paw edema model. Compounds 2d and 2i were screened for their antiproliferative activity towards 60 human cancer cell lines, displaying mild activity toward the renal cancer cell line UO-31. Copyright
- Yaseen, Shafiya,Ovais, Syed,Bashir, Rafia,Rathore, Pooja,Samim, Mohammed,Singh, Surender,Nair, Vinod,Javed, Kalim
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p. 491 - 498
(2013/07/26)
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- Palladium-catalyzed chemoselective decarboxylative ortho acylation of benzoic acids with α-oxocarboxylic acids
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Palladium-catalyzed chemoselective decarboxylative cross coupling of benzoic acids with α-oxocarboxylic acids was realized via an arene sp 2 C-H functionalization process. This work represents the first example of transition-metal-catalyzed cro
- Miao, Jinmin,Ge, Haibo
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supporting information
p. 2930 - 2933
(2013/07/26)
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- 2-Hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic Acid with Inbuilt β-NHydroxy-γ-keto-Acid pharmacophore as HCV NS5B polymerase inhibitors
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The inbuilt 2-N-hydroxy-1-oxo-3-carboxylic acid of isoquinolone was designed as pyrophosphate mimic for hepatitis C NS5B polymerase. Various 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid derivatives 11a-p were synthesized and evaluated as HCV NS5B polymerase inhibitors. Compound 11c exhibited moderate inhibitory potency based on the inorganic pyrophosphate generation (IC50 = 9.5 μM) and based on NTP incorporation by NS5B enzyme (IC50 = 5.9 μM). Compound 11c demonstrated antiviral activity (EC50 = 15.7 μM) and good selectivity in HCV genotype 1b replicon Ava.5 cells. Compound 11c reduced the interaction of NTP to NS5B polymerase. Docking model showed that 11c situated in similar orientation to the bound uridine triphosphate in the active site of NS5B polymerase. As a result, 2-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid was disclosed as a novel inbuilt β-Nhydroxy-γ-keto-acid pharmacophore for HCV NS5B polymerase inhibitors.
- Deore,Chen,Chen,Chang,Chuang,Chern,Wang,Chern
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body text
p. 613 - 624
(2012/07/28)
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- Decarboxylative C-H arylation of benzoic acids under radical conditions
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A decarboxylative radical cyclization reaction has been developed for the synthesis of fluorenones. The reaction uses Ag(I)/K2S 2O8 to oxidatively decarboxylate an aroylbenzoic acid to an aryl radical, which undergoes cyclization to afford fluorenone products in good yield.
- Seo, Sangwon,Slater, Mark,Greaney, Michael F.
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supporting information; scheme or table
p. 2650 - 2653
(2012/07/27)
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- A rapid and efficient access to diaryldibenzo[b,f][1,5]diazocines
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2-Benzoylbenzoyl azides undergo facile cyclization under acidic conditions to give substituted dibenzo[b,f][1,5]-diazocines in good yields. This approach shortens the synthetic steps toward these compounds as compared with conventional methods. The mechanism of the diazocine synthesis is assumed to proceed by an unprecedented intermolecular [2 + 2] cyclization.
- Wang, Xiao,Li, Jianzhong,Zhao, Na,Wan, Xiaobo
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supporting information; experimental part
p. 709 - 711
(2011/04/24)
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- C-ARYL GLYCOSIDE COMPOUNDS FOR THE TREATMENT OF DIABETES AND OBESITY
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This invention relates to a compound of generic formula (I): (I) as well as a pharmaceutically acceptable salt thereof, a tautomer, optical isomer or a mixture of optical isomers in any proportion, in particular a mixture of enantiomers, and particularly a racemate mixture, in particular for use thereof as a drug, notably in the treatment of diabetes.
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Page/Page column 90
(2009/10/30)
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- Efficient synthesis of isobenzofuran-1(3H)-ones (Phthalides) and selected biological evaluations
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The studies presented here deal with the convenient and efficient one-step conversion of o-alkylbenzoic acids into their corresponding isobenzofuran-1 (3H)-ones (phthalides) using NaBrO3/NaHSO3 in a two-phase system. A range of o-alkylbenzoic acids was used with the object of getting a variety of phthalide derivatives as multipurpose biologically active compounds. Seventeen phthalides have been synthesized and tested for cytotoxicity, antibacterial and antifungal activities. Some of these compounds showed promising cytotoxic effects against Artemia salina. Compounds 4j-4p were highly active against Gram-negative and Gram-positive bacteria among all tested compounds. In the fungicidal assay, the compounds showed a broad spectrum of activity against six fungi. All compounds were characterized via elemental analysis, UV, IR, mass and-NMR spectroscopy. ECV · Editio Cantor Verlag.
- Bayer, Ernst,Hayat, Safdar,Atta-Ur-Rahman,Choudhary, M. Iqbal,Khan, Khalid Mohammed,Shah, Syed Tasadaque Ali,Imran-Ul-Haq,Anwar, M. Usman,Voelter, Wolfgang
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p. 588 - 597
(2007/10/03)
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- Non-Peptidic Small-Molecule Inhibitors of the Single-Chain Hepatitis C Virus NS3 Protease/NS4A Cofactor Complex Discovered by Structure-Based NMR Screening
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NMR-based screening of a customized fragment library identified 16 small-molecule hits that bind weakly (KD ≈ 100 μM to 10 mM) to substrate binding sites of the NS4A-bound NS3 protease of the hepatitis C virus (HCV). Analogues for five classes of NMR hits were evaluated by a combination of NMR and biochemical data yielding SAR and, in most cases, optimized hits with improved potencies (KD ≈ KI ≈ 40 μM to mM). NMR chemical shift perturbation data were used to establish the binding location and orientation of the active site directed scaffolds in these five analogue series. Two of these scaffolds, which bind the enzyme at the proximal S1-S3 and S2′ substrate binding sites, were linked together producing competitive inhibitors of the HCV NS3 protease with potencies in the micromolar range. This example illustrates that the low molecular weight scaffolds discovered from structure-based NMR screening can be optimized with focused structure-guided chemistry to produce potent nonpeptidic small-molecule inhibitors of the HCV NS3 protease.
- Wyss, Daniel F.,Arasappan, Ashok,Senior, Mary M.,Wang, Yu-Sen,Beyer, Brian M.,Njoroge, F. George,McCoy, Mark A.
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p. 2486 - 2498
(2007/10/03)
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- Tricyclic alkylamides as melatonin receptor ligands with antagonist or inverse agonist activity
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This work reports the design and synthesis of novel alkylamides, characterized by a dibenzo[a,d] cycloheptene nucleus, as melatonin (MLT) receptor ligands. The tricyclic scaffold was chosen on the basis of previous quantitative structure-activity studies on MT1 and MT2 antagonists, relating selective MT2 antagonism to the presence of an aromatic substituent out of the plane of the MLT indole ring. Some dibenzo seven-membered structures were thus selected because of the noncoplanar arrangement of their benzene rings, and an alkylamide chain was introduced to fit the requirements for MLT receptor binding, namely, dibenzocycloheptenes with an acylaminoalkyl side chain at position 10 and dibenzoazepines with this side chain originating from the nitrogen atom bridging the two phenyl rings. Binding affinity at human cloned MT1 and MT2 receptors was measured by 2[125I] iodomelatonin displacement assay and intrinsic activity by the GTPγS test. The majority of the compounds were characterized by higher affinity at the MT2 than at the MT 1 receptor and by very low intrinsic activity values, thus confirming the importance of the noncoplanar arrangement of the two aromatic rings for selective MT2 antagonism. Dibenzocycloheptenes generally displayed higher MT1 and MT2 affinity than dibenzoazepines. N-(8-Methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-ylmethyl)propionamide (4c) and -butyramide (4d) were the most selective MT2 receptor antagonists of the series, with MT2 receptor affinity comparable to that of melatonin and as such among the highest reported in the literature for MLT receptor antagonists. The acetamide derivative 4b produced a noticeable reduction of GTPγS binding at MT2 receptor, thus being among the few inverse agonists described.
- Lucini, Valeria,Pannacci, Marilou,Scaglione, Francesco,Fraschini, Franco,Rivara, Sivia,Mor, Marco,Bordi, Fabrizio,Plazzi, Pier Vincenzo,Spadoni, Gilberto,Bedini, Annalida,Piersanti, Giovanni,Diamantini, Giuseppe,Tarzia, Giorgio
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p. 4202 - 4212
(2007/10/03)
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- An alternative method for the synthesis of γ-lactones by using cesium fluoride-celite/acetonitrile combination
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A variety of 2-(1-bromoalkyl) benzoic acids 4 undergo intramolecular nucleophilic substitution reaction when treated with a CsF-Celite as solid base in acetonitrile under reflux condition to give the corresponding cyclized phthalides in moderate to very good yield. These 2-(1-bromoalkyl) benzoic acids 4 are formed by the α-bromination of 2-alkylbenzoic acids 3 using N-bromosuccinimide and a catalytic amount of α,α′ -azoisobutyronitrile in carbon tetrachloride under reflux.
- Khan, Khalid Mohammed,Hayat, Safdar,Zia-Ullah,Atta-ur-Rahman,Iqbal-Choudhary,Maharvi, Ghulam Murtaza,Bayert, Ernst
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p. 3435 - 3453
(2007/10/03)
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- A novel carbocationic species paired with tetrakis(pentafluorophenyl)borate anion in catalytic aldol reaction
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The aldol reaction of several aldehydes with silyl enol ethers proceeded smoothly to give the corresponding aldols in good to high yields at -78 °C by using 1.0 mol% of a novel cationic species with tetrakis(pentafluorophenyl)borate anion.
- Mukaiyama, Teruaki,Yanagisawa, Manabu,Iida, Daisuke,Hachiya, Iwao
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p. 606 - 607
(2007/10/03)
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- Friedel-crafts alkylation and acylation in the absence of solvent
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A short and efficient synthetic route, for alkylation and acylation of aromatic compounds in the absence of solvent is developed. According to the reaction system and conditions used, different alkyl-, and acyl arenes are obtained in moderate to good yields. The structures are assigned by 1H and 13C NMR spectroscopy.
- Ghiaci,Asghari
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p. 2213 - 2220
(2007/10/03)
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- Aryl-fused and hetaryl-fused-2,4-diazepine and 2,4-diazocine antiarrhythmic agents
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Aryl-fused- and hetaryl-fused-2,4-diazepines of formula XXXVI, benzodiazocines of formula XXX, benzodiazepines of formula II STR1 δ-aminoamides of formula III and aryldimethanamines of formula XXXVII STR2 wherein A is an aryl or hetaryl ring; R1 is hydrogen, alkyl, aryl or hetaryl; R2 is hydrogen, alkyl, substituted alkyl, or aryl; R3 is alkyl, aryl, aralkyl or heteroatom substituted alkyl or aralkyl; R4 is hydrogen or alkyl; R5 is hydrogen, alkyl, aryl or hetaryl; R6 is hydrogen, alkyl, alkoxy, halogen or a fused benzene ring; R9 is hydrogen, alkyl, or substituted alkyl; and R10 is hydrogen, alkyl, or substituted alkyl. The invention further relates to processes for the preparation of, pharmaceutical compositions containing, and methods of treating cardiac arrhythmia with the compounds of formulas XXXVI, XXX, II, III, and XXXVII.
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- A Novel Series of Selective, Non-Peptide Inhibitors of Angiotensin II Binding to the AT2 Site
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The availability of peptide and non-peptide Ang II receptor antagonists has permitted the study of Ang II receptor heterogeneity.It is now widely recognized that there are at least two distinct Ang II receptor subtypes.AT1 receptors are selective in their recognition of agents such as losartan, DuP 532,L-158,809,SKF108566, and similar non-peptides.To date, all of the well-known actions of Ang II in mammals are blocked by the AT1 selective antagonists such as losartan and are thus designated as being mediated by the AT1 receptor.Although there have been reports of functional activity mediated through AT2 sites, the pharmacological role for the AT2 receptor has not yet been elucidated.Herein, we report the chemistry and SAR on a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids which have selective affinity for AT2 receptors.The most potent of which (19) has an IC50 of 30 nM for the AT2 receptor in the rat adrenal radioligand binding assay.
- VanAtten, Mary K.,Ensinger, Carol L.,Chiu, Andrew T.,McCall, Dale E.,Nguyen, Tam T.,et al.
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p. 3985 - 3992
(2007/10/02)
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- Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation. 1. 2-[2-(1-imidazolyl)alkyl]- 1(2H)-phthalazinones
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A number of 4-substituted 2-[ω-(1-imidazolyl)alkyl]-1(2H)-phthalazinones were synthesized in order to develop agents possessing both thromboxane A2 synthetase inhibitory and bronchodilatory activities. The pharmacological evaluation of these compounds disclosed that they have both activities to various extents. Both activities were slightly dependent on the length of the 2-substituents and largely affected by the nature of the 4-substituents. Compounds bearing phenyl and thienyl groups exhibited relatively high and well-rounded activities. Among these compounds, 12j and 15f were found to be the most effective agents having well-rounded activities in vitro and in vivo. Introduction of a carboxyl group reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone 18b was of particular interest because of unexpectedly high in vivo activities in spite of an absence of significant in vitro activities.
- Yamaguchi,Kamei,Koga,Akima,Kuroki,Ohi
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p. 4052 - 4060
(2007/10/02)
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- Thermally reversible organic solvent gels
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Stable, thermally reversible gels of organic solvents and a gelling agent having the formula wherein R1 is an anthracene analogue or substituted anthracene analogue, n is zero or a whole number from 2 to 20, and R2 is cholesteryl and cholestanyl or a derivative of cholesteryl or cholestanyl, processes for producing same, and novel anthracene analogue cholesteryl and cholestanyl esters and derivatives.
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