- Palladium-catalyzed ortho-arylation of benzoic acid derivatives via C-H bond activation using an aminoacetic acid bidentate directing group
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A highly efficient protocol for the palladium-catalyzed ortho-arylation of benzoic acid derivatives by aryl iodides is described with an aminoacetic acid based N,O bidentate directing group. This protocol can be applied to various benzoyl aminoacetic acids and aryl iodides with both electron-donating and electron-withdrawing groups. Remarkably, the nature of a new directing group drives selective C-H bond activation to afford only monoarylation products in good to excellent yields.
- Zhou, Xiaomeng,Wang, Qing,Zhao, Weihua,Xu, Songsong,Zhang, Wei,Chen, Junmin
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- Kinetics and Mechanisms of the Aminolysis of N-Hydroxysuccinimide Esters in Aqueous Buffers
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Rate constants for the aminolysis of the N-hydroxysuccinimide (NHS) ester of p-methoxybenzoic acid, in aqueous buffer systems (20percent dioxane), have been determined under pseudo-first-order conditions.For the amines studied (pKa = 7.60-11.1), the data fit the rate expression kobsd - kOH--> = k1free.This rate equation is in contrast to the two-term rate equation (kobsd = k1 + k22) obtained for this reaction in anhydrous dioxane (Cline, G.W.; Hanna, S.B.J.Am.Chem.Soc 1987, 109, 3087) and is suggestive of a disproportionate decrease in the catalyzed vs the uncatalyzed reaction path upon changing from a nonaqueous to an aqueous solvent system.The correlation of amine basicity with the nucleophilic rate constant, k1, yields a slope βnuc = 1.0.The magnitude of βnuc, in terms of a reaction mechanism where a tetrahedral intermediate is formed in a fast preequilibrium followed by rate-determining breakdown to products, reflects the sensitivity to changes in charge accumulation in the formation of the tetrahedral intermediate.The resultant increased rate constants, with increased basicity, are due to the effect of an increased concentration of the tetrahedral intermediate.A qualitative evaluation of the literature and current data concerning the leaving ability of N-hydroxy esters, in comparison to phenyl esters (equivalent acyl groups and nucleophiles), reveals that, with leaving groups of comparable basicity, the nucleophilic rate constants for N-hydroxy esters are about 2 orders of magnitude greater than that for phenyl esters.
- Cline, Gary W.,Hanna, Samir B.
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- Anthranilate 4H-oxazol-5-ones: Novel small molecule antibacterial acyl carrier protein synthase (AcpS) inhibitors
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D-optimal design and Projection to Latent Structures (PLS) analysis were used to optimize screening hit 5 (B. subtilis AcpS IC50: 15 μM, B. subtilis MIC: >200 μM) into a series of 4H-oxazol-5-one, small molecule, antibacterial, AcpS inhibitors. Specifically, 15, 16 and 18 show μM or sub-μM AcpS inhibition (IC50s: 15: 1.1 μM, 16: 1.5 μM, 18: 0.27 μM) and moderate antibacterial activity (MICs: 12.5-50 μM) against B. subtilis, E. faecalis ATCC, E. faecalis VRE and S. pneumo+.
- Gilbert, Adam M.,Kirisits, Matthew,Toy, Patrick,Nunn, David S.,Failli, Amadeo,Dushin, Elizabeth G.,Novikova, Elena,Petersen, Peter J.,Joseph-Mccarthy, Diane,McFadyen, Iain,Fritz, Christian C.
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- Synthesis and Biological Evaluation of New Diarylpyrazole and Triarylimidazoline Derivatives as Selective COX-2 Inhibitors
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New series of diarylpyrazoles 8a–f and triarylimidazoline-5-ones 11a–g were synthesized and evaluated for their in vitro cyclooxygenase-1 (COX-1) and COX-2 inhibitory activity and in vivo anti-inflammatory activity. The synthesized compounds showed good selectivity for COX-2; compounds 8a, 8d, 8f, 11a, and 11c exhibited the highest COX-2 selectivity indexes (SI = 4.77–5.43) compared to the reference drug celecoxib (SI = 7.8). All compounds showed good in vivo anti-inflammatory activity, especially compounds 8a, 8f, 11c, and 11d, which also showed some similarities to the time interval pattern of celecoxib at all different time intervals (1, 3, and 6 h).
- Abdellatif, Khaled R.A.,Abdelgawad, Mohamed A.,Labib, Madlen B.,Zidan, Taha H.
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- Synthesis and evaluation of new phenyl acrylamide derivatives as potent non-nucleoside anti-HBV agents
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As a continuation of our previous work, a series of new phenyl acrylamide derivatives (4Aa-g, 4Ba-t, 5 and 6a-c) were designed and synthesized as non-nucleoside anti-HBV agents. Among them, compound 4Bs could potently inhibit HBV DNA replication in wild-type and lamivudine (3TC)/entecavir resistant HBV mutant strains with IC50 values of 0.19 and 0.18 μM, respectively. Notably, the selective index value of 4Bs was above 526, indicating the favorable safety profile. Interestingly, unlike nucleoside analogue 3TC, 4Bs could significantly inhibit 3.5 kb pgRNA expression. Molecular docking study revealed that 4Bs could fit well into the dimer-dimer interface of HBV core protein by hydrophobic, π–π and H-bond interactions. Considering the potent anti-HBV activity, low toxicity and diverse anti-HBV mechanism from that of nucleoside anti-HBV agent 3TC, compound 4Bs might be a promising lead to develop novel non-nucleoside anti-HBV therapeutic agents, and warranted further investigation.
- Gu, Xiaoke,Zhang, Yinpeng,Zou, Yueting,Li, Xin,Guan, Mingyu,Zhou, Qingqing,Qiu, Jingying
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- Synthesis, characterization and anticancer activity of (5,1-substituted)-3-(indoline-4-(thiophene- 2-yl-methylene)-2-(p-tolyl)-2-methylene)-4,3-dihydro-1h-imidazole-5-one derivatives
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The synthesis of novel imidazole-5-one derivatives (5a-j) was allowed in a conventional method by way of Erlenmeyer and Schiff base mechanism. Compound 2a was synthesized by Erlenmeyer reaction of N-(4-methoxy benzoyl)glycine with 2-thiophene-carboxaldehyde in the presence of acetic anhydride and anhydrous sodium acetate. Finally, it undergoes dehydration reaction with Schiff bases of isatin derivatives (4a-j) to yield final compounds 5a-j. The organic potentials of the newly synthesized imidazole-5-one derivatives have been evaluated for their in vitro anticancer activity by MTT assay method. It against MCF-7 cells as comparison with doxorubicin popular drug. The synthesized compounds 5e, 5f and 5j exhibited excellent anticancer activity against MCF-7 cell lines.
- BAYYA, CHANDRAPRAKASH,MANDA, SARANGAPANI
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p. 2027 - 2032
(2021/08/24)
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- Nickel-Catalyzed Asymmetric Hydrogenation of 2-Amidoacrylates
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Earth-abundant nickel, coordinated with a suitable chiral bisphosphine ligand, was found to be an efficient catalyst for the asymmetric hydrogenation of 2-amidoacrylates, affording the chiral α-amino acid esters in quantitative yields and excellent enantioselectivity (up to 96 % ee). The active catalyst component was studied by NMR and HRMS, which helped us to realize high catalytic efficiency on a gram scale with a low catalyst loading (S/C=2000). The hydrogenated products could be simply converted into chiral α-amino acids, β-amino alcohols, and their bioactive derivatives. Furthermore, the catalytic mechanism was investigated using deuterium-labeling experiments and computational calculations.
- Chen, Jianzhong,Gridnev, Ilya D.,Hu, Yawen,Li, Bowen,Zhang, Wanbin,Zhang, Zhenfeng
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supporting information
p. 5371 - 5375
(2020/02/15)
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- Piperidine thiazole derivative containing bisamide structure as well as preparation method and application thereof
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The invention discloses a piperidine thiazole derivative containing a bisamide structure, and also discloses a preparation method of the piperidine thiazole derivative and application of the piperidine thiazole derivative as a sterilization agent and an insecticide. The invention provides the novel piperidine thiazole derivative containing the bisamide structure; the preparation method is simpleand convenient; the piperidine thiazole derivative can be used for preventing and treating cucumber gray mold, rice sheath blight diseases and potato late blight diseases, has good sterilization activity, can be used for preventing and treating insect pest of armyworm, black bean aphid, tetranychus telarius linne and the like, and lays the foundation for the invention and development of piperidinethiazole pesticides.
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Paragraph 0027
(2019/02/03)
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- Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails
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Being the primary sulfonamide among the most efficient zinc binding group (ZBG) to design inhibitors for the metallo-enzymes carbonic anhydrases (CA, EC 4.2.1.1), herein, we propose an investigation on four physiologically important human (h) CAs (hCA I, II, IV, and IX) with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails. The effect of the functionalisation of the sulfonamide group with five different substitution patterns, namely acetyl, pyridine, thiazole, pyrimidine, and carbamimidoyl, was evaluated in relation to the inhibition profile of the corresponding primary sulfonamide analogues. With most of these latter being nanomolar inhibitors of all four considered isoforms, a totally counterproductive effect on the inhibition potency can be ascribed to N1-functionalisations of the ZBG primary sulfonamide structure with pyridine, thiazole, and pyrimidine moieties. On the other hand, incorporation of less hindered groups, such as sulfonylacetamides and sulfonylguanidines, maintained a certain degree of activity dependent on the tailing moiety, with KIs spanning in the low micromolar range.
- Awadallah, Fadi M.,Bua, Silvia,Mahmoud, Walaa R.,Nada, Hossam H.,Nocentini, Alessio,Supuran, Claudiu T.
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p. 629 - 638
(2018/03/26)
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- Alpha-amino acrylate microbicide and preparation method and application thereof
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The invention provides an alpha-amino acrylate microbicide and a preparation method and application thereof. The alpha-amino acrylate microbicide has a specific chemical structure formula shown as a formula I, and the formula I is shown in the description. The alpha-amino acrylate microbicide has the advantages that by utilizing the design principle of pesticide molecules, a medical leading compound with anti-coronavirus activity is performed with structure modification of agricultural plant virus-resisting activity, a series of alpha-amino acrylate derivatives is designed and synthesized, and particularly, the alpha-amino acrylate derivative containing piperidine ring is synthesized; the known compound is used as a positive reference compound to systematically screen the biology activity; a plurality of high-efficiency anti-virus leading molecules are provided for the developing of new pesticides, and the positive meaning is realized for the reduction application of the pesticide and the protection of environment ecology.
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- Design, Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of Imidazolone Fused Pyrazolo[1,5-a]pyrimidine Derivatives
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A novel series of imidazolone fused pyrazolo[1,5-a]pyrimidine derivatives has been designed and synthesized using a convergent approach, and the structures of these compounds were confirmed by 1H NMR, 13C NMR, ESI-MS, and IR analyses. These new compounds were tested for their in vitro antiproliferative activity using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Out of the 20 derivatives prepared in the current study, compounds 8h, 8n, and 8r exhibited good anticancer activities tested against HeLa cells and HepG2 cells. However, the in vitro anticancer activity of compound 8r against HeLa, HepG2, and MCF-7 cell lines is superior to the marketed drugs Paclitaxel and SAHA.
- Ajeesh Kumar,Bodke, Yadav D.,Gowda, Ashwath N.,Sambasivam, Ganesh,Bhat, Kishore G.
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p. 1904 - 1924
(2017/05/29)
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- A Facile and Efficient Synthesis of 4-Arylidene-2-phenyl-5(4H)-oxazolones and Their Antimicrobial Evaluation against Selected Human and Phytopathogens
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A simple and convenient method has been developed for the synthesis of a series of 2-(4-substituted phenyl)-4-(substituted arylidene)-1,3-oxazol-5-ones (5a–j) via reactions of hippuric acid with differently substituted aromatic aldehydes (4a–j) in sodium acetate, potassium acetate, calcium acetate, and ammonium acetate, respectively, which were tested for their efficiency as catalysts in both conventional and microwave-assisted synthetic methods in presence of 4 ? zeolites. The title compounds were evaluated for their antimicrobial properties against selected human pathogens (bacterial and fungal) and phytopathogens (fungal) and were compared with standard drugs. The results of the study are reported.
- Voosala, Christopher,Kilaru, Padma Suhasini,Dasari, Uday Kumar
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p. 909 - 916
(2016/11/23)
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- Catalytic Asymmetric Synthesis of anti-α,β-Diamino Acid Derivatives
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A novel approach to chiral anti-α,β-diamino acid derivatives through tandem orthogonal organocatalysis has been developed. Chiral phosphoric acid catalysts control the chemo-, regio-, and stereoselective addition of hydroxylamines to alkylideneoxazolones, while a phosphine catalyst promotes the isomerization of Z- alkylideneoxazolones to the more reactive E- alkylideneoxazolones. (Chemical Equation Presented).
- Izumi, Sanae,Kobayashi, Yusuke,Takemoto, Yoshiji
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supporting information
p. 696 - 699
(2016/03/01)
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- Synthesis and biological testing of (5Z)-2-aryl-5-arylmethylidene-3,5-dihydro-4H-imidazol-4-ones as antimitotic agents
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Compounds interacting with cell protein tubulin and microtubules represent an important type of antimitotic agents. A series of tubulin-targeted 2-aryl-4-benzoyl-imidazoles were reported to possess high cytotoxicity, and so, we prepared a series of structural isomers of these to be evaluated as antimitotic agents. The synthesis of the novel (Z)-2-aryl-5-arylmethylidene-3,5-dihydro-4H-imidazol-4-ones involved coupling of substituted hippuric acids with aromatic aldehydes. Subsequent conversion of the resulting oxazolones to the corresponding imidazolones was carried out under microwave irradiation in the presence of urea and ammonium acetate. The cytotoxicity of the majority of the compounds to human epithelial carcinoma cancer cell line A549 was in the sub-micromolar range and was found to be more sensitive to the substituents on the 5-arylmethylidene fragment than on the 2-aryl ring in general. The cytotoxicities of the synthesized compounds were lower than those of the previously reported isomeric 2-aryl-4-benzoyl-imidazoles, and the basic structure–activity relationships in the isomeric pairs were different. Synthesized (5Z)-5-[(4-bromophenyl)methylidene]-2-(4-methylphenyl)-3,5-dihydro-4H-imidazol-4-one, which had the highest cytotoxicity (IC50?~?440?nM) in the series of novel compounds, had a definite cytostatic effect on the A549 cells, but its antiproliferative properties were not linked to action on the microtubules. This would be an interesting lead compound for additional investigation into the mechanism of cytostatic action, and further structural optimization.
- Beloglazkina, Anastasia A.,Wobith, Birgit,Barskaia, Elena S.,Zefirov, Nikolay A.,Majouga, Alexander G.,Beloglazkina, Elena K.,Zyk, Nikolay V.,Kuznetsov, Sergei A.,Zefirova, Olga N.
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p. 1239 - 1249
(2016/07/06)
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- Synthesis of di- and tri-substituted imidazole-4-carboxylates via PBu3-mediated [3+2] cycloaddition
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Some new di- and trisubstituted imidazole-4-carboxylates were prepared from amidoacetic acids 3 in the present report. The key step to establish such imidazole- 4-carboxylates stemmed from the PBu3-mediated [3+2] cycloaddition between in situ-generated Δ2-oxazolinone 4 and ethyl cyanoformate6. Our results indicated that trisubstituted imidazoles 7-20 were afforded in better yields than those of disubstituted imidazoles 21-27. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Hsu, Mei-Yuan,Dietrich, Justin,Hulme, Christopher,Shaw, Arthur Y.
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p. 1538 - 1542
(2013/05/21)
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- Lewis acid catalyzed formation of 3-amino-3-carboxy-tetrahydroquinoline derivatives via tandem 1,5-hydride transfer/cyclization process
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A Sc(OTf)3-catalyzed intramolecular tandem 1,5-hydride transfer/cyclization process to construct 3-amino-3-carboxy-tetrahydroquinoline derivatives has been developed. The methodology gives access to a range of relatively complex tetrahydroquinolines (tetracyclic and pentacyclic heterocycles bearing spirocyclic skeleton and two stereogenic centers) in good to excellent yields with diastereoselectivities ranging from 57:43 to 73:27. The synthetic utility of the method was also demonstrated by an efficient ring opening derivatization reaction.
- Han, Wen-Yong,Zuo, Jian,Wu, Zhi-Jun,Zhang, Xiao-Mei,Yuan, Wei-Cheng
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p. 7019 - 7025
(2013/07/26)
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- Design, synthesis and antidiabetic evaluation of oxazolone derivatives
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A series of ten novel (2a-j) 4-arylidine 2-[4-methoxy phenyl] oxazol-5-one derivatives were synthesized and assayed in vivo to investigate their antidiabetic activities by streptozotocin-induced model in rat. These derivatives showed considerable biological efficacy when compared to rosiglitazone, a potent and wellknown antidiabetic agent as a reference drug. All the compounds were effective, amongst them 2d shows more prominent activity at 50 mg/k.g.p.o. The experimental results are statistically significant at P 0.01 level. Indian Academy of Sciences.
- Mariappan,Saha,Datta, Sriparna,Kumar, Deepak,Haldar
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experimental part
p. 335 - 341
(2012/05/20)
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- A convenient method for synthesis of 5-chloro-2-aryloxazole-4-carbaldehyde with vilsmeier reagent
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A convenient method for synthesis of 5-chloro-2-aryloxazole-4-carbaldehyde 3 in moderate to good yields had been developed via the Vilsmeier reaction of readily available N-arylglycine 2 at 100 °C, provided a novel route for the construction of nitrogen heterocycles. A series of these compounds were synthesized by this method and optimization of conditions was performed. The Japan Institute of Heterocyclic Chemistry.
- Jin, Can,Chen, Jun,Su, Weike
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experimental part
p. 153 - 161
(2011/04/21)
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- Phenylpropenamide derivatives: Anti-hepatitis B virus activity of the Z isomer, SAR and the search for novel analogs
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Phenylpropenamides have been reported to be a class of non-nucleoside inhibitors of the hepatitis B virus (HBV). This class of compounds was explored with the objective of developing potent anti-HBV agents, with a novel mechanism of action, that could be combined with nucleos(t)ide analogs currently used to treat HBV infection. To accomplish this objective a series of substituted arylpropenamide derivatives were prepared and the E and Z geometrical isomers were separated. The structural identity of each of the E and Z isomers was determined by single crystal X-ray crystallography. Contrary to previous reports, the activity of this class of molecules resides in the Z isomer. Further structure-activity relationship studies around the active Z isomer identified compounds that displayed potent antiviral activity against HBV with EC90 value of approximately 0.5 μM in vitro. Attempts to develop ring constrained analogs did not lead to active HBV inhibitors.
- Wang, Peiyuan,Naduthambi, Devan,Mosley, Ralph T.,Niu, Congrong,Furman, Phillip A.,Otto, Michael J.,Sofia, Michael J.
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scheme or table
p. 4642 - 4647
(2011/09/12)
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- Structural effects of N-aromatic acyl-amino acid conjugates on their deconjugation in the cecal contents of rats: Implication in design of a colon-specific prodrug with controlled conversion rate at the target site
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N-aromatic acyl-amino acid conjugates possess a colon-targeted property, implying that such conjugates are stable and are not absorbable until reaching the large intestine in which they are microbially converted (hydrolysed) to the parent drugs that are therapeutically active. To investigate the structural effect of N-aromatic acyl-amino acid conjugates on the large intestinal deconjugation, the hydrolysis of various N-aromatic acyl-amino acid conjugates was examined in the cecal contents. On incubation of conjugates with glycine,d or/andl forms of alanine or phenylalanine in the cecal contents, the conjugates withd amino acids were not hydrolysed. The other conjugates are susceptible to the hydrolysis, the rates of which decreased as the size of the substituent on the 2-position of the amino acids increased. The conjugates with alkyl analogs (2-4 carbons) of glycine and taurine were resistant to the hydrolysis, while taurine- and glycine-conjugates were hydrolysed effectively. The hydrolysis of N-aromatic acyl-glycine conjugates was enhanced by para-substitution of electron withdrawing groups on the aromatic acyl moiety and vice versa for electron-donating groups. While a methyl, methoxy or chloro group on the ortho-position retarded the hydrolysis, a hydroxyl group on the position accelerated it. Our data may provide useful information for the design of a colon-specific prodrug with controlled conversion rate in the large intestine.
- Kong, Hyesik,Kim, Hyunjeong,Do, Heejeong,Lee, Yonghyun,Hong, Sungchae,Yoon, Jeong-Hyun,Jung, Yunjin,Kim, Young Mi
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experimental part
p. 343 - 354
(2012/04/10)
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- Synthesis and study of some compounds containing oxazolone ring, showing biological activity
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Synthesis of the oxazolone ring has been performed by the condensation of 4-substituted alkoxy benzoyl glycine with appropriate 4-substituted alkoxy benzaldehyde, in the presence of acetic anhydride and anhydrous sodium acetate. The antibacterial activity has been checked against Micrococcus luteus and Escherichia coli and antifungal activity against Alternaria alternate and Phoma multirostata for all the compounds. The cytotoxicity has been checked against the monocots barley seeds: Hordeum vulgare L and dicots moong seeds; Phaseolus aureus. The compounds having electron releasing group exhibit antibacterial activity. Compounds with nitro group cause total inhibition of seed germination, exhibiting cytotoxic behaviour. The structures of the synthesized compounds have been characterized by elemental analysis and spectral data and the purity of the compounds has been checked by TLC method.
- Tandel,Mammen, Denni
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p. 932 - 937
(2008/12/23)
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- 4-(2 phenylthiazol-5-yl)-1, 4-diazabicyclo-[3.2.2]nonane deirvatives, preparation and therapeutic use thereof
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Compound corresponding to the general formula (I) in which R1, R2, R3, R4 and R5 each represent a hydrogen or halogen atom or a nitro, amino, trifluoromethyl, trifluoroalkoxy, cyano, hydroxyl, (C
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Page/Page column 2
(2008/06/13)
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- 2-Acylpyridazin-3-ones: Novel mild and chemoselective acylating agents for amines
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2-Acyl-4,5-dichloropyridazin-3-ones served as excellent novel N-acylating reagents for amines under neutral conditions in organic solvent. They are convenient, chemoselective and easy to handle stable N-acylating reagents of amines.
- Kang, Young-Jin,Chung, Hyun-A,Kim, Jeum-Jong,Yoon, Yong-Jin
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p. 733 - 738
(2007/10/03)
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- Ethanolysis of 4- (N, N-dimethylaminomemylene)-2-aryl-2-oxazolin-5-ones with sodium ethoxide in ethanol at reflux temperature: Unusual formation of N-acyl-α-amino acids
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The ethanolysis of 4-(N, N - dimethylaminomethylene)-2-aryl-2-oxazolin-5-ones 1 with sodium ethoxide in ethanol at reflux temperature leads to the formation of N-acyl-α-amino acids 3. Further, the reaction of 4-hydroxymethylene-2-phenyl-2-oxazolin-5 one 4 with sodium ethoxide in ethanol at reflux temperature also gives product 3a. The plausible mechanism has been proposed.
- Singh, Ram S.
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p. 1296 - 1299
(2007/10/03)
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- An unusual ground-state stabilization effect and origins of the α- effect in aminolyses of Y-substituted phenyl X-substituted benzoates
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Second-order rate constants have been measured spectrophotometrically for the reactions of X-C6H4CO2C6H4-Y with a series of primary amines in H2O containing 20 mol% DMSO at 25.0 ± 0.1°C. The reactivity increases as the substituent (X and Y) becomes a stronger electron-withdrawing group. The σ+ constants give better Hammett correlation than σ constants for the reactions of 4-nitrophenyl X-substituted benzoates with glycylglycine (glygly) and hydrazine (NH2NH2), indicating that the ground-state stabilization effect is unusually significant on the reaction rates. The reactions of X-C6H4CO2C6H4-Y with glygly and NH2NH2 appear to proceed through the same mechanism, but the degree of leaving-group departure and the negative charge developed in the acyl moiety at the rate-determining TS is considered to be more significant for the glygly system than the NH2NH2 system based on β(1g) and ρ(x) values. The magnitude of the α-effect is observed to be not always dependent on the β(nuc) value but dependent on the electronic nature of the substituent X and Y, i.e., an electron-donating substituent increases the α-effect, while an electron-withdrawing one decreases the α-effect. The present study has led to the conclusion that the ground-state effect is important for the reaction rates but it is not solely responsible for the α-effect, and the intramolecular H-bonding interactions (4) are proposed for the cause of the increasing or decreasing α-effect trends observed in the present system.
- Um, Ik-Hwan,Chung, Eun-Kyung,Lee, So-Mi
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p. 729 - 737
(2007/10/03)
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- Synthesis and aldose reductase inhibitory activity of benzoyl-amino acid derivatives
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A series of N-(4-methoxy, 4-fluoro, 4-trifluoromethyl and 4-nitrobenzoyl)-L-amino acids was synthesized and their inhibitory activity towards bovine lens aldose reductase (ALR2) was tested.
- Benvenuti, Stefania,Severi, Fabio,Costantino, Luca,Vampa, Gabriella,Melegari, Michele
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p. 439 - 442
(2007/10/03)
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- Polymer-Supported Mitsunobu Ether Formation and its Use in Combinatorial Chemistry
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Aromatic hydroxy acids have been attached to a polymeric solid support and the phenolic hydroxy groups have been reacted with a variety of primary and secondary alcohols under the conditions of the Mitsunobu reaction (triphenylphosphine and diethyl azodicarboxylate) in tetrahydrofuran.In most cases the reaction provided a nearly quantitative yield of alkyl aryl ethers, as determined after cleaving theproduct from the resin.To demonstrate that the polymer-supported Mitsunobu reaction is useful for combinatorial library synthesis, we synthesized a number of model compounds and a simple three randomization step library composed of 4,200 different compounds.
- Krchnak, Viktor,Flegelova, Zuzka,Weichsel, Aleksandra S.,Lebl, Michal
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p. 6193 - 6196
(2007/10/02)
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- Synthesis and in Vitro Aldolase Reductase Inhibitory Activity of Compounds Containing an N-Acylglycine Moiety
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A number of N-benzoylglycines (6), N-acetyl-N-phenylglycines (7), N-benzoyl-N-phenylglycines (8), and tricyclic N-acetic acids (9-12) were synthesized as analogues of the N-acylglycine-containing aldolase reductase inhibitors alrestatin and 2-oxoquinoline-1-acetic acid.Derivatives of 6, which represent ring-simplified analogues of alrestatin, are very weak inhibitors of aldolase reductase obtained from rat lens, producing 50percent inhibition only at concentrations exceeding 100 μM.Compounds of series 7 were designed as ring-opened analogues of the 2-oxoquinolines.While this derivatives are more potent than compounds of series 6 (IC 50s of 6-80 μM), they are less active than the corresponding 2-oxoquinolines.Analogues of series 8 were designed as hybrid structures of both alrestatin and the 2-oxoquinoline-1-acetic acids.These compounds are substantially more potent than compounds of series 6 and 7 and display inhibitory activities comparable to or greater than alrestatin or the 2-oxoquinolines (IC 50s of 0.1-10 μM).Of the rigid analogues of 8, the most potent derivative is benzoxindol (12) with an IC 50 of 0.67 μM, suggesting that fusion of the two aromatic rings of 8 in a coplanar conformation may optimize affinity for aldose reductase in this series.
- DeRuiter, Jack,Swearingen, Blake E.,Wandrekar, Vinay,Mayfield, Charles A.
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p. 1033 - 1038
(2007/10/02)
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- Composition containing a penem or carbapenem antibiotic and the use of the same
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Administration of an N-acylated amino acid in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid derivative and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially.
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- Composition containing a penem or carbapenem antibiotic
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Administration of an N-acylated amino acid in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid derivative and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially. The composition may be prepared by simple mixing.
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- ETUDE CINETIQUE DE L'AMINOLYSE EN MILIEU NON AQUEUX D'ESTERS MODELES DE PEPTIDYL-t-ARN; INFLUENCE D'UN GROUPE HYDROXYLE VOISIN
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n-Butylaminolysis of cis 2-hydroxy-cyclopentyl benzoylglycinate (a simple model of peptidyl-t-RNA) in MeCN occurs ca 300 times faster than that of cyclopentyl benzoylglycinate.This acceleration caused by the neighbouring cis 2-hydroxy group is considerabl
- Julia, Marc,Mestdagh, Helene
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p. 327 - 337
(2007/10/02)
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- A Chromogen Produced in the Reaction of Glycine Derivatives with Acetic Anhydride and Pyridine
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The yellow chromogen produced in the assay of glutathione or glycocholic acid by their reactions with acetic anhydride and pyridine was found to be a conjugated compound containing pyridylidene and 2-oxazoline rings.The structure was confirmed by hydrolysis of the chromogen to 4-aminomethylpyridine.The same chromogen was formed with benzoylpeptides having C-terminal glycine.Keywords - chromogen; Glutathione; glycocholic acid; spectrophotometry; 2-oxazoline; pyridylidene
- Hirota, Kazuhiro,Ikeda, Mikiko
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p. 3100 - 3104
(2007/10/02)
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- Structure-Reactivity Studies on the Equilibrium Reaction between Phenolate Ions and 2-Aryloxazolin-5-ones: Data Consistent with a Concerted Acyl-Group-Transfer Mechanism
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The rate and equilibrium constants for the reaction between phenolate anions and 2-aryloxazolin-5-ones have been measured as a function of the structures Ar and Ar'.The change in "effective" charge on both phenol-leaving oxygen and endocyclic oxygen from ground to transition state, as determined from the relevant Broensted parameters, is substantial and essentially additive consistent with a concerted displacement mechanism.The stepwise mechanism requires a small change in effective charge on the phenol oxygen because departure of phenolate ion from the tetrahedral intermediate cannot be rate limiting.Hydroxide ion attack on the C-5 atom of the oxazolinone to yield a benzoylglycine has a Hammett ?- dependence which can only arise from a concerted displacement; the rate-limiting step for the stepwise mechanism is the addition of hydroxide and the transition state of the rate-limiting step will therefore not involve much endocyclic C-O bond fission.An inverse deuterium oxide solvent isotope effect indicates that the observed general-acid catalysis has a specific-acid/nucleophilic mechanism; both hydroxide and oxonium ion catalysis are demonstrated by using 18O-labeling experiments to involve nucleophilic attack at the carbonyl (C-5) center.The equilibrium constant for reaction of azide ion with 2-phenyloxazolin-5-ones has been measured; it is suggested that the absence of racemization during azide coupling in peptide synthesis is related to the very unfavorable equilibrium constant for oxazolinone formation compared with that of activated oxygen esters.
- Curran, Terence C,Farrar, Charles R.,Niazy, Omima,Williams, Andrew
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p. 6828 - 6837
(2007/10/02)
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- SYNTHESIS AND SPECTRAL-LUMINISCENCE PROPERTIES OF 2-ARYL-4-BENZYLIDENE-5-OXAZOLONES
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A number of 2-aryl-4-benzylidene-5-oxazolones was obtained by condensation of benzaldehyde with N-acylglycines.The absorption and fluorescence spectra in chloroform at 77 deg K were measured.The spectral characteristics of the investigated and previously
- Krasovitskii, B. M.,Lysova, I. V.,Afanasiadi, L. Sh.
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p. 701 - 703
(2007/10/02)
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