bluuebunny/crossref_metadata_2025 huggingface dataset:
Creep analysis of high concrete‐faced rockfill dam
Authors: Wei Zhou , Xiaolin Chang , Chuangbing Zhou , Xinghong Liu
Published: April 2009

The focus of the present study of a concrete‐faced rockfill dam (CFRD) is the time‐dependent deformation problem of rockfill, especially under a high confining pressure. In this paper, a new creep constitutive model for rockfill is introduced. A numerical realization step and algorithm applied to the analysis using the general finite element method is also presented for the creep model. The numerical simulation result of the creep model is compared with data from a laboratory triaxial creep test. It is concluded that the creep model can describe the real creep characteristics and mechanical behavior of rockfill. In studying the stress and deformation behavior of the high rockfill dam, and considering the creep effect, the creep model is applied in performing creep analysis of the Shuibuya CFRD with 200 m high in China, now the highest constructed CFRD in the world. In comparing the creep numerical simulation results with those of previous analyses that did not consider the creep effect, the deformation of the dam exhibits an evident increment, and the rockfill creep has an obvious influence on the deformation and stress of the concrete‐face slab. The prediction of the final maximum settlement was 2.09 m for the Shuibuya Dam, with the rockfill creep effect in accord with the creep parameters of the triaxial creep test. Copyright © 2009 John Wiley & Sons, Ltd.
Bmp2 and Bmp4 genetically interact to support multiple aspects of mouse development including functional heart development
Authors: Uchimura Takashi , Komatsu Yoshihiro , Tanaka Momo , McCann Kelly L. , Mishina Yuji
Published: April 2009

Bone morphogenetic proteins (BMPs) have multiple roles during embryogenesis. Current data indicate that the dosage of BMPs is tightly regulated for normal development in mice. Since Bmp2 or Bmp4 homozygous mutant mice show early embryonic lethality, we generated compound heterozygous mice for Bmp2 and Bmp4 to explore the impact of lowered dosage of these BMP ligands. Genotyping pups bred between Bmp2 and Bmp4 heterozygous mice revealed that the ratio of adult compound heterozygous mice for Bmp2 and Bmp4 is much lower than expected. During embryogenesis, the compound heterozygous embryos showed several abnormalities, including defects in eye formation, body wall closure defects, and ventricular septal defects (VSD) in the heart. However, the ratio of the compound heterozygous embryos was the same as expected. Caesarean sections at E18.5 revealed that half of the compound heterozygotes died soon after birth, and the majority of the dead individuals exhibited VSD. Survivors were able to grow to adults, but their body weight was significantly lower than control littermates. They demonstrated progressive abnormalities in the heart, eventually showing a branched leaflet in atrioventricular valves. These results suggest that the dosage of both BMP2 and 4 is critical for functional heart formation during embryogenesis and after birth. genesis 47:374–384, 2009. © 2009 Wiley‐Liss, Inc.
Lmx1b‐expressing cells in the mouse limb bud define a dorsal mesenchymal lineage compartment
Authors: Qiu Qiong , Chen Haixu , Johnson Randy L.
Published: April 2009

Lmx1b‐lacZ expression (blue) highlights dorsal‐restricted expression in limb bud mesenchyme of the mouse embryo. See the paper by Qiu and Johnson in this issue.
Determination of organophosphorus pesticides by capillary electrophoresis‐inductively coupled plasma mass spectrometry with collective sample‐introduction technique
Authors: Yang GuiDi , Xu XueQin , Shen MinCong , Wang Wei , Xu LiangJun , Chen GuoNan , Fu FengFu
Published: April 2009

A new method for the determination of organophosphorus pesticides using CE‐ICP‐MS with collective sample‐introduction technique has been developed in this study. The method has been successfully used to separate and determine dimethoate, trichlorfon and glyphosate with an RSD of <5% for migration times (n=6) and <4% for peak areas (n=6). The experimental results showed that the collective sample‐introduction considerably reduced the makeup volume and the dilution of analyte, and eventually resulted in a much lower detection limit and a much better electrophoretic resolution. The peak widths and the detection limits of dimethoate, trichlorfon and glyphosate obtained with this method are 15–17 s and 0.05–0.07 μg/mL (as compound), respectively. Using this method, we have successfully separated and determined dimethoate, trichlorfon and glyphosate in vegetable sample with a recovery of 90–96%.
Effect of salicylic acid and diclofenac on the medium‐chain and long‐chain acyl‐CoA formation in the liver and brain of mouse
Authors: Kasuya Fumiyo , Kazumi Maya , Tatsuki Takao , Suzuki Risa
Published: April 2009

Medium‐chain and long‐chain acyl‐CoA esters are key metabolites in fatty acid metabolism. Effects of salicylic acid on thein vivoformation of acyl‐CoAs in mouse liver and brain were investigated. Further, inhibition of the medium‐chain and long‐chain acyl‐CoA synthetases by salicylic acid and diclofenac was determined in mouse liver and brain mitochondria. Acyl‐CoA esters were analyzed by liquid chromatography–tandem mass spectrometry. The amounts of medium‐chain acyl‐CoAs (C6, C8and C10) were less than long‐chain acyl‐CoAs (C16:0, C18:0, C18:1and C20:4) in both liver and brain. The administration of salicylic acid decreased the levels of both the medium‐chain (C6, C8and C10) and long‐chain acyl‐CoAs (C16:0, C18:0, C18:1and C20:4) in liver. In brain, however, only long‐chain acyl‐CoAs were decreased. The level of salicylyl‐CoA detected in brain was about 12% of that in liver. Salicylic acid had a strong inhibitory activity (IC50 = 0.1 mm) for the liver mitochondrial formation of hexanoyl‐CoA from hexanoic acid, whereas diclofenac was weak (IC50 = 4.4 mm). In contrast, diclofenac (IC50 = 1.4 mm) inhibited the liver mitochondrial long‐chain acyl‐CoA synthetases more potently than salicylic acid (IC50 = 25.5 mm). Similar inhibitory activities for the acyl‐CoA synthetases were obtained in the case of the brain and liver mitochondria, except for the weak inhibition of brain medium‐chain acyl‐CoA synthetases by salicylic acid (IC50 = 1.8 mm). These findings suggest that salicylic acid and diclofenac exhibit different mechanisms of inhibition of fatty acid metabolism depending on the length of the acyl chain and tissues, and they may contribute to the further understanding of the toxic effects associated with these drugs. Copyright © 2009 John Wiley & Sons, Ltd.
Therapist responsiveness to child engagement: flexibility within manual‐based CBT for anxious youth
Authors: Chu Brian C. , Kendall Philip C.
Published: April 2009

Therapy process research helps delineate common and specific elements essential to positive outcomes as well as develop best practice training protocols. Child involvement and therapist flexibility were rated in 63 anxious youth (ages 8–14) who received cognitive–behavioral therapy. Therapist flexibility, defined as therapist attempts to adapt treatment to a child's needs, was hypothesized to act as an engagement strategy that serves to increase child involvement during therapy. Flexibility was significantly related to increases in later child engagement, which subsequently predicted improvement in posttreatment diagnosis and impairment. Therapist flexibility was not associated with earlier measures of child engagement, so a mediation model could not be supported. It was also hypothesized that the impact of flexibility would be greatest for cases who began treatment highly disengaged (i.e., early involvement would moderate the effect of flexibility). Basic descriptive data supported this model, but formal analyses failed to confirm. Further descriptive analyses suggest therapists employ a range of adaptations and a profile of flexible applications within a manual‐based treatment is provided. Treatment, measurement, and dissemination issues are discussed. © 2009 Wiley Periodicals, Inc. J Clin Psychol: 65: 1–19, 2009.
The synthesis of ω‐dialkylaminoalkylaminopyrazino[2,3‐d]‐, pyrido[2,3‐d]‐, imidazo[4,5‐c]‐ and imidazo[4,5‐d]pyridazines
Authors: Patel Natu R. , Rich William M. , Castle Raymond N.
Published: April 2009

The synthesis of 5‐chloro‐8‐(ω‐dialkylaminoalkylamino)pyrazino[2,3‐d]pyridazine (II) proceeded smoothly when 5,8‐dichloropyrazino[2,3‐d]pyridazine (I) was allowed to react with ω‐dialkylaminoalkylamines. Similarly, the reaction of 5,8‐dichloropyrido[2,3‐d]pyridazine (IV) with ω‐dialkylaminoalkylamines gave the two expected products 8‐chloro‐5‐(ω‐dialkylaminoalkylamino)pyrido[2,3‐d]pyridazine (V) and 5‐chloro‐8‐(ω‐dialkylaminoalkylamino)pyrido[2,3‐d]pyridazine (VI) in a 2:3 ratio. 4,7‐Dichloroimidazo[4,5‐d]pyridazine (XII) was found to be much less reactive towards nucleophilic substitutions and more vigorous conditions resulted in disubstituted products (XIII). 7‐Chloroimidazo[4,5‐c]pyridazine (XVIII) was also found to be much less reactive towards nucleophilic substitution. In both of these cases one of the imidazole nitrogen atoms was blocked by a tetrahydropyranyl group which increased the reactivities and led to the desired monosubstituted products XVII from XII and in the latter case the expected products (XIX).
Pyrimidines. XXI. 1‐(Tetrahydro‐2‐furyl)pyrimidines
Authors: Noell C. Wayne , Cheng C. C.
Published: April 2009

A number of 1‐(tetrahydro‐2‐furyl)uracils, cytosines and related compounds were synthesized by a modified Hilbert‐Johnson method from 2‐chlorotetrahydrofuran and the corresponding 2,4‐dimethoxypyrimidines. The relative stability in acid of tetrahydrofuryl and tetrahydropyranyl moieties in compounds of this type was discussed. 2‐Oxo‐4‐methoxy‐1,2‐dihydropyrimidine, a compound which has been erroneously reported, has now been prepared and its structure confirmed by conversion into cytosine.
The polymerization of difluorodiazirine
Authors: Ogden Paul H. , Mitsch Ronald A.
Published: April 2009

Pyrolysis or ultraviolet photolysis of difluorodiazirine in the presence of boron trifluoride produced polydifluoromethylene. Like polymethylene derived from diazomethane, the polydifluoromethylene so produced possesses “living polymer” properties. The mechanism of polymerization is discussed and is thought to involve the formation of a linear intermediate.
The nitrobenzo [b] thiophenes
Authors: Boswell D. E. , Brennan J. A. , Landis P. S. , Rodewald P. G.
Published: April 2009

Syntheses, and infrared and nuclear magnetic resonance spectral data for the six mononitrobenzo[b] thiophenes are described. Sulfonation of benzo[b] thiophene has been demonstrated to produce the 2‐ and 3‐isomers.
Picrylamino‐substituted heterocycles. II. Furazans
Authors: Coburn Michael D.
Published: April 2009

This paper describes the synthesis of the various picrylamino‐ and nitro‐substituted furazans and bifurazanyls. Except for 3,4‐bis(picrylamino)furazan, which was obtained by nitrating 3,4‐dianilinofurazan, the picrylaminofurazans were prepared by condensing the appropriate amino‐furazan with picryl fluoride in the presence of triethylamine. The various aminofurazans were oxidized with peroxytrifluoroacetic acid to the corresponding nitro derivatives.
Tautomer chemistry of thiazolidines. 1‐Thia‐4‐azaspiro[4,5] decanes
Authors: Stacy Gardner W. , Strong Philip L.
Published: April 2009

The thiazolidine, 1‐thia‐4‐azaspiro[4,5] decane (Ia), which is derived from cyclohexanone and 2‐aminoethanethiol (X), forms a thiazolidone (VIII) with mercaptoacetic acid more slowly and in lower yield than with 2‐phenylthiazolidine, a case reported previously. A thiazolidine which is related to a non‐conjugate chain tautomer such as Ic, might be expected to behave in this way. Alkylation, as another possible example of tautomer chemistry, was studied, and N‐, S‐, and C‐alkylation were all observed under varying circumstances. Thus, thiazolidine la undergoes alkylation with methyl iodide in ethanol to form the N‐methylthiazolidine (IIa), and in sodium‐liquid ammonia to give the S‐methyl derivative (III). In the latter case, alkylation occurs with reductive cleavage. Although no trace of other tautomer derivatives (IV, V) was to be found in the methyl iodide alkylation, I with acrylonitrile did in fact give C‐alkylation. An analytically pure mixture of tautomers was obtained, from which 2‐oxocyclohexanepropionitrile (VI) was isolated on hydrolysis. In a manner similar to the formation of III, IIa was S‐alkylated by treatment with sodium‐liquid ammonia followed by benzyl chloride to give a saturated product (XVII). Although such a process might be identified with a chain tautomer (IIb), the evidence is to the contrary, since the intermediate (XIV), which might be involved in such a process, fails to undergo a similar reduction with sodium‐liquid ammonia. A greatly improved procedure for the preparation of thiazolidine (XI, 86% yield) is also reported.
Synthesis of possible metabolites of chlorpromazine. II. 3‐, 8‐ and 9‐hydroxychlorpromazine
Authors: Nodiff Edward A. , Oda Noriichi , Hayazaki Takanori , Ina Shuichiro , Ito Toshiyuki , Nishibe Sansei , Ueda Taisei , Suzuki Kenji , Hausman Martin , Manian Albert A.
Published: April 2009

The title compounds have been prepared as analytical standards for the identification of chlorpromazine metabolites in biological materials. Unequivocal structural proof of key compounds was accomplished by using at least two unrelated syntheses for each one. Resistance of some phenothiazines to preparation via classic Smiles rearrangement is discussed. More examples are offered of halogen‐induced Smiles rearrangement. A rare example of phenothiazine polymorphism is presented.
A direct, stereoselective synthesis of optically active conhydrines
Authors: Fodor Gabor , Bauerschmidt Eberhard
Published: April 2009

2‐Pyridylethylcarbinol (I) has been resolved and the antipodes hydrogenated as free bases. The (+) form gave (+) conhydrine (II) while the (‐) form afforded the levorotatory base stereoselectively with minor contamination of the other epimer. Hydrogenation of racemic I as well as of 2‐pyridyl ethyl ketone in acid solution led formerly to the mixture of both racemates.
Reaction of certain isocyanates with azomethines. Evidence for a new heterocyclic adduct
Authors: Chupp John P. , Landwehr Helen K.
Published: April 2009

The preparation of triazinone (I) from certain isocyanates and N‐alkyl azomethines was found to proceed easily without catalyst, particularly in refluxing chlorobenzene. The physical and chemical properties, including n.m.r. spectra of the oily triazinones, are contrasted with the newly discovered solid adducts arising from low temperature reaction of azomethine and chlorophenyl isocyanates. From stoichiometry of the reaction, elemental analysis, molecular weight of the products, and spectral analyses, the new materials (II) were found to incorporate two isocyanate and three azomethine moieties in their molecular make‐up. The relative merits are considered for assigning II a molecular structure arising from a complex between a four and six‐membered ring (III, IV) versus a ten‐membered ring system (V, VI, VIa).
The preparation of diazine derivatives containing the ferroin group
Authors: Case Francis H.
Published: April 2009

With the idea of providing new compounds capable of chelation with metal ions, certain derivatives of diazines, containing the ferroin (NCCN) group have been prepared.
Azasteroids. v. approaches to the 14,16‐diazasteroidal ring system
Authors: Katz Lawrence E. , Popp Frank D.
Published: April 2009

Making use of Reissert compound II and Reissert compound analogue VI, benzo [f]quinoline has been converted into the 14,16‐diazasteroidal ring system. A number of reactions in this ring system are discussed.
The synthesis and some reactions of 2,3‐substituted 1‐phenylbenzo[f]quinoline
Authors: Chan Tze‐Lock , Hamer Jan
Published: April 2009

A series of 2,3‐substituted 1‐phenylbenzo[f]quinolines was synthesized by the Friedlander condensation of 1‐benzoyl‐2‐naphthylamine with β‐keto esters. Some chemical transformations of these compounds and the preparation of 13H‐benzo[f]indeno[2,1‐c]quinoline‐13‐one and its 9‐methyl derivative are described.
The reaction of 2‐(ω‐chloroalkyl)benzimidazoles with thiourea. Studies on heterocyclic compounds. I
Authors: Ogura H. , Itoh T. , Tajika Y.
Published: April 2009

By reaction of the appropriate 2‐(ω‐chloroalkyl)benzimidazoles with thiourea, 2‐(α‐mercaptoalkyl)benzimidazoles (IV) have been prepared. The attempted preparation of 2‐(β‐ and γ‐mercaptoalkyl)benzimidazoles failed. β‐Elimination was observed by alkaline treatment of S‐[2‐(2‐benzimidazolyl)‐propyl]isothiuronium chloride (VII), whereas 2‐(γ‐chlorobutyl)benzimidazoles did not give an isothiuronium chloride.
Thiophene series. Note IX . The absence of secondary steric effects in nucleophilic substitutions of thiophene derivatives: Kinetics of the reactions of 2‐bromo‐3,5‐dinitrothiophene and 2‐bromo‐3,5‐dinitro‐4‐methylthiophene with piperidine
Authors: Spinelli Domenico , Guanti Giuseppe , Dell'Erba Carlo
Published: April 2009

The kinetics of the reactions of piperidine with 2‐bromo‐3,5‐dinitrothiophcne (IV) and 2‐bromo‐3,5‐dinitro‐4‐methylthiophene (III) have been measured in methanol, ethanol and benzene.

Molecular model predictions were confirmed when the kinetic results (kIV/kIII ≅ 2) demonstrated, for the first time, the absence of secondary steric effects for nucleophilic substitutions in thiophene compounds.
Crystal and molecular structure of 6‐(p‐bromobenzoyl)‐6‐azabicyclo[3.1.0]hexane
Authors: Zacharis H. M. , Trefonas L. M.
Published: April 2009

The molecular structure of 6‐(p‐bromobenzoyl)‐6‐azabicyclo[3.1.0]hexane has been determined by a single crystal, three‐dimensional x‐ray study. The compound crystallizes in the monoclinic space group (P) with four molecules in a unit cell of dimensions a = 8.83, b = 10.15, c = 12.63 ± 0.02Å and β = 94°55′ ± 5′. The aziridine ring is eis fused to the cyclopentane ring with the two rings together in a boat conformation. The fusion angle of the two rings is 110.8°. The aziridine ring has all angles of 60 ±1° and all bond distances of 1.48 ± 0.03Å. The cyclopentane ring has alternately long (1.61 ± 0.04Å) and short (1.52 ± 0.02Å) distances. Non‐fusion angles in the cyclopentane ring are 106.0 ± 0.5°. Other molecular parameters are as anticipated. The 844 independent reflections obtained were refined to a final value of R = 0.116 using full‐matrix least squares techniques.
1‐Aryl‐4,6‐diamino‐1,2‐dihydro‐s‐triazines. Contrasting effects on intestinal helminths, bacteria, and dihydrofolic reductase
Authors: Capps David B. , Bird Orson D. , Elslager Edward F. , Gavrilis Zoe B. , Roush Jane A. , Thompson Paul E. , Vaitkus John W.
Published: April 2009

The preparation of a variety of novel 1‐aryl‐4,6‐diamino‐1,2‐dihydro‐s‐triazines is described. These compounds exhibit an array of contrasting effects on intestinal helminths, bacteria, and dihydrofolic reductase. It is concluded that potent anthelmintic activity among the dihydro‐triazines is not dependent solely on the bulky‐substituent hypothesis advanced by other investigators, and indeed cannot reliably be predicted on this basis.
Pyridazines. IV. The synthesis and some reactions of acetylpyridazines
Authors: Nakagome Takenari , Castle Raymond N.
Published: April 2009

Two 3‐acetylpyridazines have been prepared. N‐Oxidation of 3‐acetylpyridazine (6) gave only 3‐acetylpyridazine 1‐oxide (7). During the N‐oxidation of 3‐acetyl‐6‐methoxypyridazine (10), three primary products, namely, 3‐acetyl‐6‐methoxypyridazine 1‐oxide (12), 3‐acetyl‐6‐methoxy‐pyridazine 2‐oxide (13), 3‐acetylpyridazin‐6‐one (14) and an artifact, 3‐methoxypyridazine 1‐oxide (15) were obtained. Furthermore, it has been shown that 3‐methoxypyridazine 1‐oxide (15) can be obtained in quantitative yield by treatment of 3‐acetyl‐6‐methoxypyridazine 2‐oxide (13) with dilute sodium hydroxide solution at room temperature. This represents a novel deacylation reaction. Nitration of 3‐acetylpyridazine 1‐oxide, (7) gave 3,4‐bis(3′‐pyridazinoyl)furoxan 1′,1′‐dioxide (19) rather than a simple nitration product. 3‐Acetyl‐pyridazine (6) and 3‐acetyl‐6‐methoxypyridazine (10) also gave furoxans (22 and 23) upon nitration.
Aromaticity in heterocyclic systems V. Bromination studies of certain purines, pyrrolo[3,2‐d]pyrimidines and pyrazolo[4,3‐d]pyrimidines
Authors: Cassidy Frederick , Olsen Richard K. , Robins Roland K.
Published: April 2009

The bromination of certain selected purines, pyrrolo[3,2‐d]pyrimidines and pyrazolo[4,3‐d]‐pyrimidines has been studied and the reactivity of these systems compared. Displacement of a carboxyl group by bromine was noted in the case of 6‐carboxypyrrolo[3,2‐d]‐2,4‐pyrimidinedione. In contrast to xanthine, 2,6‐diethoxypurine readily brominated at position 8. Pyrazolo‐[4,3‐d]‐7‐pyrimidone was readily brominated at position 3.
Heterocyclic tautomerisms. III. An investigation of the 2‐arylbenzothiazoline‐2‐(benzylideneamino)thiophenol tautomerism. Part 3
Authors: Goetz Frederick J.
Published: April 2009

The electronic spectra of various, substituted 2‐arylbenzothiazoline (1)‐2‐(benzylideneamino)‐thiophenol (II) tautomers were studied in order to determine what species were present in ethanol solution. In every case examined the absorption spectra closely resembled those of the correspondingly substituted 3‐methyl‐2‐arylbenzothiazolines (III) and differed markedly from those of corresponding 2‐(benzylideneamino)phenyl methyl sulfides (IV). These results indicate that, under the conditions examined, the 2‐arylbenzothiazoline tautomer (I) predominates. Infrared spectra determined or solid samples of series I‐II, III and IV were entirely in accord with structure I.
The synthesis of 5,10‐dihydro‐ and 2,3,5,10‐tetrahydrothiazolo‐[3,2‐b] [2,4]benzodiazepines, 1,2,3,4,7,12‐hexahydrobenzothiazolo‐[3,2‐b] [2,4] benzodiazepine, and 9,14‐dihydro‐6H‐[1]benzothiopyrano‐[4′,3′:4,5]thiazolo[3,2‐b] [2,4] benzodiazepine via 1,2,4,5‐Tetrahydro‐3H‐2,4‐benzodiazepine‐3‐thione
Authors: Elslager Edward F. , Worth Donald F. , Haley Neil F. , Perricone S. C.
Published: April 2009

Catalytic reductive scission of phthalazine (II) utilizing a two‐stage palladium‐Raney nickel procedure afforded o‐xylene‐α,α′‐diamine (III) in 97% yield. Treatment of III with carbon disulfide gave [o‐(aminomethyl)benzyl]dithiocarbamic acid (IV), which upon thermal cyclization furnished 1,2,4,5‐tetrahydro‐3H‐2,4‐benzodiazepine‐3‐thione (V). Reaction of V with 1,2‐dibromoethane, chloro‐2‐propanone, ethyl 2‐chloroacetoacetate, ethyl chloroacetate, and ethyl 2‐bromohexanoate gave 2,3,5,10‐tetrahydrothiazolo[3,2‐b][2,4]benzodiazepine (VII) and substituted 5,10‐dihydrothiazolo[3,2‐b][2,4]benzodiazepines (Villa and b, IX, and X), respectively. Condensation of V with 2‐chlorocyclohexanone and 3‐bromothiochroman‐4‐one afforded 1,2,3,4,7,12‐hexahydrobenzothiazolo[3,2‐b][2,4]benzodiazepine (XII) and 9,14‐dihydro‐6H‐[1]benzothiopyrano[4′,3′:4,5]thiazolo[3,2‐b][2,4]benzodiazepine(XIll). None of the compounds possessed appreciable biological activity.
Flavinyl peptides. I. Synthesis of flavinyl‐aromatic amino acids
Authors: Föry Werner , Mackenzie Robert E. , Mccormick Donald B.
Published: April 2009

The syntheses of flavinyl peptides, in which L‐tryptophan, L‐tyrosine, or L‐phenylalanine are attached via peptide linkage to the isoalloxazine system with ω‐carboxyalkyl groups in position 3 or 10, are described. Lumiflavin was carboxymethylated by known methods to yield N‐3‐carboxymethyllumiflavin. Oxidation of 10‐ω‐hydroxyhexyl‐, 10‐ω‐hydroxypentyl‐, 10‐ω‐hydroxybutyl‐, and 10‐formylmethylflavins gave the corresponding 10‐ω‐carboxyalkylflavins. The 10‐ω‐carboxyethylflavin was obtained by condensation of 2‐amino‐4,5‐dimethyl‐N‐ω‐carboxyethylaniline with alloxan. Activations of the carboxyl group of the flavins were achieved with N,N′‐carbonyldiimidazole and p‐nitrophenyltrifluoroacetate to form the corresponding acyl imidazoles and p‐nitrophenyl esters. 10‐Carboxymethylflavin was hydrogenated to form 10‐carboxymethyldihydroflavin and activated by carbodiimide. Reaction of the carboxy‐activated flavins with the appropriate amino acid methyl esters, followed by air oxidation in the case of dihydroflavin, gave the corresponding flavinyl peptides.

Interaction of the flavin with aromatic amino acids results in a broadening of the visible flavin absorption towards the green, without the appearance of discrete new maxima, and in quenching of the flavin fluorescence. The fluorescence efficiency increases with increasing numbers of methylene groups in the flavin side chain. The nonlinear dependency of fluorescence quenching versus number of methylene groups indicates that different types of intramolecular interactions are involved.
NMR proof of the structure of 4‐aminoquinolines and pyridines
Authors: Craig John C. , Pearson D. E.
Published: April 2009

Nmr spectra of a number of 4‐N‐alkylaminoquinolines and 4‐N‐alkylaminopyridines show coupling between hydrogen of the amino group and α‐hydrogen on the alkyl group. No such coupling would be observed if the hydrogen were on heterocyclic nitrogen. Other nmr characteristics in the benzenoid region suggest that all simple 4‐aminoquinolines and 4‐aminopyridines have the amino structure.
Preparation and ultraviolet absorption spectra of the isomeric naphthobenzothiophenes and naphthobenzofurans
Authors: Campaigne E. , Osborn S. W.
Published: April 2009

Naphtho[2,1‐b]benzothiophene has been synthesized unequivocally by the ring closure of 2‐phenylmercapto‐1‐tetralone, followed by dehydrogenation of the resulting dihydro derivative. The other isomeric naphthobenzothiophenes have been prepared by modifications of known methods and their ultraviolet absorption spectra have been compared.

Condensation of α‐naphthol with 2‐chlorocyclohexanone leads to 7,8,9,10‐tetrahydronaphtho‐[1,2‐‐6]benzofuran, which can be readily dehydrogenated with selenium to naphtho[1,2‐b]‐benzofuran. The ultraviolet spectra of the naphthobenzofurans are reported, and compared to their sulfur analogs.
A mechanistic study of the synthesis of meso‐tetraphenylporphin
Authors: Adler Alan D. , Sklar Larry , Longo Frederick R. , Finarelli John D. , Finarelli Margaret G.
Published: April 2009

In continuation of an earlier preliminary study, some further physical and synthetic studies on the homogenous phase condensation of pyrrole and benzaldehyde to ms‐tetraphenylporphin in acidic media were undertaken. The role of atmospheric oxygen in the reaction was studied in some detail. The effects of acidity, solvent, concentration, and other constraints on both the rate and yield of the reaction were also investigated. Details of the mechanism, including possible intermediate structures, have been clarified and a reaction scheme accounting for the data is presented.
Proton resonance spectra of heterocycles. VI. Chromanones, thiochromanones, and 2,3‐dihydro‐4‐quinolones
Authors: Katritzky A. R. , Ternai B.
Published: April 2009

The nmr spectra of the title compounds and some substituted derivatives are recorded and discussed. It is concluded that 3‐halogeno substituents probably occupy largely pseudo axial positions whereas a 3‐methyl group is predominantly pseudo equatorial.
Chemistry of thienopyridines. IV. Syntheses of 5‐substituted thieno[2,3‐b] pyridines
Authors: Klemm L. H. , Zell Reinhard
Published: April 2009

Chemical transformations on 5‐acetylthieno[2,3–6] pyridine produced 5‐NH2, 5‐CO2H, and 5‐CH2 CO2H substituents. The 5‐amino compound underwent facile diazotization (plus Sand‐meyer reaction), Schiff's base formation, and acylation. Treatment of the derived 5‐bromo compound with potassium amide in liquid ammonia gave a mixture of 4‐amino (major) and 5‐amino isomers. Nmr spectral data are reported for the 5‐substituted thieno [2,3‐b] pyridine system.
Steroid derivatives of purine‐6(1H)‐thione (1a‐c)
Authors: Carroll F. I. , Philip Abraham , Ferguson Anna M. , Wall Monroe F.
Published: April 2009

The products obtained as a result of the alkylation of purine‐6(1H)‐thione, and 6‐alkylthiopurines with steroidal‐21‐(p‐bromobenzenesullonates) (H) and 3‐methoxy‐16α‐bromoestra‐1,3,5 (10)‐tricne‐17‐one (IV) is reported. The ratio of 9‐alkylated to 7‐alkylated purine in the alkylation of 6‐methylthiopurine (VI) is presented. The use of the S‐diphenylmethylprotecling group in the syntheses of sensitive 9‐steroidal‐9H‐purine‐6(1H)‐thiones is discussed.
Infrared and nuclear magnetic resonance properties of benzoyl derivatives of five‐membered monoheterocycles and determination of aromaticity indices
Authors: Jeon Kyu Ok , Jun Jung Ho , Yu Ji Sook , Lee Chang Kiu
Published: April 2009

Benzophenones, 2‐benzoylthiophenes, 2‐benzoylpyrroles, and 2‐benzoylfurans, which have substituents at m‐ and p‐positions of the benzoyl ring were prepared and their ir and nmr spectra were obtained in 0.1 M chloroform‐d solution. The chemical shift values of each series were plotted against the Hammett substituent parameters to give good correlation, with the exception of the ortho‐Hs and ‐Cs. The slopes as well as the differences in chemical shift gave sets of meaningful values for the indices of aromaticy.
Synthesis of novel 1,4‐dihydropyrido[3′,2′:5,6]thiopyrano[4,3‐c]‐pyrazoles and 5H‐pyrido[3′,2′:5,6]thiopyrano[4,3‐d]pyrimidines as potential antiproliferative agents
Authors: Primofiore Giampaolo , Marini Anna Maria , Da Settimo Federico , Salerno Silvia , Bertini Daniele , Dalla Via Lisa , Magno Sebastiano Marciani
Published: April 2009

The synthesis of new planar derivatives characterized by the presence of a pyridothiopyranopyrazole or pyridothiopyranopyrimidine nucleus, carrying a substituted aryl group, is reported. The novel 1,4‐dihydropyrido[3′,2′:5,6]thiopyrano[4,3‐c]pyrazole derivatives were obtained by condensation of 2,3‐dihydro‐3‐hydroxymethylenethiopyrano[2,3‐b]pyridin‐4(4H)‐ones with appropriate hydrazines. The preparation of 2‐substituted pyrido[3′,2′:5,6]thiopyrano[4,3‐d]pyrimidines was accomplished from the intermediate 2,3‐dihy‐dro‐3‐dimethylaminomethylenethiopyrano[2,3‐b]pyridin‐4(4H)‐ones by reaction with the appropriate binucleophile amidines. The antiproliferative activity of some new products was tested by an in vitro assay on human tumour cell lines (HL‐60 and HeLa), but none of them showed any significant effects in the tests performed. Accordingly, linear flow dichroism measurements indicated their inability to form a molecular complex with DNA.
New trans/cis tetrahydroisoquinolines. 2. trans‐ and cis‐3‐(1‐methyl‐1h‐pyrrol‐2‐yl)‐1‐(2H)‐oxo‐2‐phenethyl‐1,2,3,4‐tetrahydroisoquino‐lin‐4‐carboxylic acids and subsequent transformations
Authors: Stoyanova M. P. , Kozekov I. D. , Palamareva M. D.
Published: April 2009

Stereochemical course of the reaction of homophthalic anhydride and N‐(1‐methyl‐1H‐pyrrol‐2‐yl‐methylidene)‐phenethylamine was studied. Mixtures of the expected trans‐ and cis‐1,2,3,4‐tetrahydroiso‐quinoline‐4‐carboxylic acids trans‐4 and cis‐4 were obtained along with by‐products 5 and 6. The ratios of all products and the diastereomers, obtained under different reaction conditions, were established by pmr. THF as a solvent and ultrasonic treatment are applied for the first time in the reaction of this type. The reaction was made diastereoselective towards any isomer. The carboxylic group of trans‐4 was transformed in four steps into various cyclic amino‐methyl groups yielding numerous new tetrahydroisoquinolinones trans‐10a‐i incorporating a given fragment of pharmacological interest. Reduction of 10a‐i was studied.
On triazoles XLVII. Synthesis of 1,3a,5,6,ωc‐pentaazacycloalka[e]acenaphthylenes
Authors: Berecz Gábor , Reiter József
Published: April 2009

To study the influence of planar or bulky cycloalkane rings attached to the 1,3a,5,6,ωc‐pentaazaacen‐aphthylenes to the reactivity of their 4‐alkylthio group toward amines ‐ an unexpected reaction observed recently at 1,3a,5,6,10c‐pentaazaacephenanthrylenes (5b, n = 4) ‐ different size 1,3a,5,6,ωc‐pentaazacyclo‐alka[e]acenaphthylenes (5a, n = 3; 5c, n = 5; 5d, n = 6; or 5e, n = 10) were synthesised and their spectral data compared with that of 5b (n = 4). Based on the analogy of the chemical shifts of carbon atoms at position 4 with that of 5b, similar electronic structure and thus a possibility of an analogous nucleophilic attack of amines was proposed and subsequently proved by a preparative method.
Quinolone analogues 6 [1‐5]. Synthesis of 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones
Authors: Kurasawa Yoshihisa , Satoh Waka , Matsuzaki Izumi , Maesaki Yuka , Okamoto Yoshihisa , Kim Ho Sik
Published: April 2009

The reaction of the quinoxaline N‐oxides 7a,b with diethyl ethoxymethylenemalonate gave the 1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 8a,b, whose reaction with N‐bromosuccinimide or N‐chlorosuccinimide afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4,4‐dicarboxylates 9a‐d. The reaction of compounds 9a‐d with hydrazine hydrate resulted in hydrolysis and decarboxylation to provide the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 10a‐d, whose reaction with nitrous acid effected oxidation to furnish the 3‐halogeno‐4‐hydroxy‐1‐methylpyridazino[3,4‐b]quinoxaline‐4‐carboxylates 11a‐d, respectively. The reaction of compounds 11a‐d with hydrazine hydrate afforded the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4‐ols 12a‐d, whose oxidation provided the 3‐halogeno‐1‐methylpyridazino[3,4‐b]quinoxalin‐4(1H)‐ones 6a‐d, respectively. Compounds 6a‐d had antifungal activities in vitro.
Synthesis of thiophene/phenylene co‐oligomers. IV. 6‐ to 8‐ring molecules
Authors: Hotta Shu , Katagiri Toshifumi
Published: April 2009

We report the synthesis of various thiophene/phenylene co‐oligomers with a total number of thiophene and benzene (phenylene) rings of 6 to 8. These compounds include a phenyl‐capped sexithiophene, a thienyl‐capped quaterphenylene, as well as block and alternating co‐oligomers. The synthesis is based on either the Suzuki coupling reaction or the direct dimerization coupling. The latter method produces symmetric molecules with an even total ring number. These reaction schemes enabled us to obtain the target compounds in high quality. Although the resulting materials are difficult to dissolve in organic solvents and therefore difficult to identify by usual 1H nmr spectroscopy, they have successfully been identified through Fourier‐transform ir spectroscopy. The specific group frequencies of ring‐stretching and out‐of‐plane deformation modes are characteristic of the substitution pattern of the individual thiophene and benzene rings.
Relative ortho‐directing power of fluorine, chlorine and methoxy group for the metalation reaction in the diazine series. Diazines XXXV
Authors: Toudic Frédéric , Turck Alain , Plé Nelly , Quéguiner Guy , Darabantu Mircea , Lequeux Thierry , Pommelet Jean Claude
Published: April 2009

The regioselectivity of the metalation of 2‐chloro‐6‐methoxypyrazine, 2‐fluoro‐6‐methoxypyrazine and 3‐fluoro‐6‐chloropyridazine was studied; the relative ortho‐directing power was F > OMe > Cl.
Design and synthesis of novel rofecoxib analogs as potential cyclooxygenase (COX‐2) inhibitors: Replacement of the methylsulfonyl pharmacophore by a sulfonylazide bioisostere
Authors: Uddin Md. Jashim , Rao P. N. Praveen , Knaus Edward E.
Published: April 2009

A group of rofecoxib analogs, having a sulfonylazide (SO2N3) substituent in place of the methanesulfonyl (SO2CH3) pharmacophore at the meta‐position viz 3‐(4‐methyl, 4‐methoxy, or 4‐ethoxyphenyl)‐4‐(3‐sulfonylazidophenyl)‐2(5H)furanone (7a‐c) and para‐position viz 3‐phenyl‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone (7d), 3‐(4‐fluoro, or 4‐chlorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone (7e‐f) of the C–4 phenyl ring, and 4‐(1‐oxido‐4‐pyridyl)‐3‐phenyl‐2(5H)furanone (12) were designed and synthesized for evaluation as selective cyclooxygenase‐2 (COX‐2) inhibitors. In vitro COX‐1/COX‐2 enzyme inhibition studies showed that 3‐phenyl‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone (7d) inhibited COX‐1 selectively (COX‐1 IC50 = 0.6659 μM; COX‐2 IC50 > 100 μM) and 3‐(4‐fluorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone (7e) inhibited both enzymes (COX‐1 IC50 = 0.8494 μM; COX‐2 IC50 = 1.7661 μM). A molecular modeling study was performed where 3‐(4‐fluorophenyl)‐4‐(4‐sulfonylazidophenyl)‐2(5H)furanone (7e) was docked in the active site of murine COX‐2 isozyme, which showed that the sulfonylazido group inserts deep into the 2°‐pocket of COX‐2 where it undergoes both H‐bonding (Gln192, Phe518) and weak electrostatic (Arg513) interactions.
Synthesis of potential selective cox‐2 enzyme inhibitors derived from ethyl ester of 2‐isothiocyanato‐5‐phenyl‐3‐thiophenecarboxylic acid
Authors: Santagati Andrea , Marrazzo Agostino , Granata Giuseppe
Published: April 2009

Derivatives containing the thieno[2,3‐d]pyrimidin‐4‐one system, potential selective COX‐2 inhibitors, were prepared starting from ethyl ester of 2‐isothiocyanato‐5‐phenyl‐3‐thiophenecarboxylic acid (2); their structural elucidation is also reported.
Synthesis of novel 3,4‐dihydropyrimidinones on water soluble solid support catalyzed by indium triflate
Authors: Shanmugam P. , Annie G. , Perumal P. T.
Published: April 2009

Syntheses of several new 3,4‐dihydropyrimidinones (DHPMs) on sodium sulfate solid support have been reported. The microwave enhanced rapid synthesis of the title compounds yielded a good percentage of the DHPMs. The catalytic activity of indium triflate enables to prepare a wide range of DHPMs. Syntheses of 2‐hydroxyphenyl, 2‐hydroxy‐4‐methoxyphenyl pendant groups on DHPMs scaffold are advantages of the present method, which are rather prone towards cyclization and the presence of free hydroxyl groups on the phenyl ring is confirmed via D2O exchange study. The mechanism of the reaction is expected to proceed via absorption of substrates on the solid support followed by promotion of the reaction by In(OTf)3 coupled with microwave irradiation.
Tetrahydrofuranylmethylamines: An efficient and simple one‐step synthesis and biological activities
Authors: Limbeck Marcus , Gündisch Daniela
Published: April 2009

Various tetrahydrofuran‐2‐ylmethylamines have been prepared in good yields by an efficient one‐step synthesis utilizing the reaction of tetrahydrofurfurylchloride with different secondary cyclic amines without any catalyst. The compounds were tested for their in vitro affinity for the (α4)2(β2)3 and α7* nicotinic acetylcholine receptor (nAChR) subtypes. Pyrrolidine, piperidine and azepane containing analogs (1a, 1b, 1c) showed Ki values in the lower micromolar range for these neuronal nAChR subtypes in rat brain.
Synthesis of 1‐nonanoyl/octadecanoyl‐4‐substituted thiosemicarbazides and substituted 1,2,4‐trizoles as biological active compounds
Authors: Colanceska‐Ragenovic Katica , Dimova Vesna , Kakurinov Vlado , Gabor Dora Molnar
Published: April 2009

4‐Alkyl/aryl‐5‐nonanoyl/octadecanoyl‐2,4‐dihydro‐3H‐1,2,4‐triazoline‐3‐thiones were synthesized as potential antimicrobial agents. The course of synthesis included the reaction of nonanoyl/octadecanoyl hydrazines with selected alkyl/aryl isothiocyanates. The prepared thiosemicarbazides gave by cyclization the required 1,2,4‐triazoles. A number of synthesized compounds were subjected to in vitro testing against two gram‐positive, two gram‐negative bacteria and two fungi.
Hypervalent iodine in synthesis 93. A facile synthesis of 2‐substituted imidazo[1,2‐a]pyrimidines by cyclocondensation of alkynyl(phenyl)iodonium salts and 2‐aminopyrimidine
Authors: Liu Zhi , Chen Zhen‐Chu , Zheng Qin‐Guo
Published: April 2009

Simple stirring of a mixture of the alkynyl(phenyl)iodonium salts 1 with 2‐aminopyrimidine 2 in chloroform under reflux for two hours in the presence of K2CO3 gave, after workup, the 2‐substituted imidazo[1,2‐α]pyrimidines 3 in moderate to good yields. A possible mechanism for the formation of 3 involves the intramolecular cyclization of the intermediate alkylidenecarbene 6.
Synthesis of water‐soluble near‐infrared cyanine dyes functionalized with [(succinimido)oxy]carbonyl group
Authors: Strekowski Lucjan , Mason Christian J. , Lee Hyeran , Gupta Rajni , Sowell John , Patonay Gabor
Published: April 2009

Two hetamethine cyanine dyes suitable for labeling of biomolecules at a primary amino group with a near‐infrared chromophore/fluorophore (λmax/(λem = 800/830 nm and 837/864 nm) have been synthesized from readily available starting materials. Despite the high molecular complexity of intermediate and final products, all these compounds have been obtained in an analytically pure form by using crystallization only.
Versatile 2‐aminothiazoles, building blocks for highly functionalised heterocycles
Authors: Kaupp Gerd , Amer Fathy A. , Metwally Mohamed Abbas , Abdel‐Latif Ehab
Published: April 2009

The reactions of quantitatively available 4‐phenyl‐ and 4‐(4‐antipyrinyl)‐2‐aminothiazole [“4‐antipyrinyl‐” is used as a short‐term for “4‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1‐H‐pyrazol‐4yl)‐”] with chloroacetyl chloride, acetic anhydride, ethyl cyanoacetate and carbon disulphide are reported. The products are transformed further by Knoevenagel condensations and coupling reactions with aromatic diazonium salts. The latter occur both at the thiazole ring and at the active methylene sites. The tautomerism of these products is studied on the basis of density functional theory calculations at the B3LYP/6‐31G* level.
Studies on pyrrolidones. An improved synthesis of N‐arylmethyl pyroglutamic acids
Authors: Bourry Anne , Akué‐Gédu Rufine , Rigo Benoit , Hénichart Jean‐Pierre , Sanz Gérard , Couturier Daniel
Published: April 2009

Low solubility of the aromatic aldehyde in a water/ethanol medium can prevent the sodium borohydride reductive alkylation of the sodium salt of glutamic acid. In that case, the reductive alkylation can be realized in methanol by using a triethylammonium salt. The uses of 2 molar equivalent of triethylammonium salt of glutamic acid for one molar equivalent of aldehyde strongly raise the yields. Cyclization of the N‐substituted glutamic acids obtained gives then N‐arylmethyl pyroglutamic acids in good yields.
Synthesis and biological activity evaluation of differently substituted 1,4‐dioxo‐3,4‐dihydrophthalazine‐2(1H)‐carboxamides and ‐carbothioamides
Authors: Cardia M. C. , Distinto S. , Maccioni E. , Bonsignore L. , Delogu A.
Published: April 2009

Differently substituted phthalic anhydrides can react either with semicarbazide or thiosemicarbazide to give respectively 1,4‐dioxo‐3,4‐dihydrophthalazine‐2(1H)‐carboxamides or 1,4‐dioxo‐3,4‐dihydrophthal‐azine‐2(1H)‐carbothioamides under mild conditions and generally with good yields. These compounds have been tested in order to evaluate their anti‐microbial activity. Furthermore a new synthetic pathway to phtha‐lazino[2,3‐b]phthalazine‐5,7,12,14‐tetraone has been devised.
Automated structure elucidation — the benefits of a symbiotic relationship between the spectroscopist and the expert system
Authors: Elyashberg Mikhail E. , Blinov Kirill A. , Martirosian Eduard R. , Molodtsov Sergey G. , Williams Antony J. , Martin Gary E.
Published: April 2009

Characteristic features of a new expert system StrucEluc are described. The system is intended for the structure elucidation of complex organic molecules using a variety of spectroscopic data including 2D NMR. We review here the results of challenging this system with over 100 structure elucidation problems where the 2D NMR peak tables presented in original journal publications provided the input data. This contribution is focused on methods to overcome difficult situations that can arise when contradictions are present in the input data and/or when the structure is underdetermined as a result of insufficient 2D NMR correlations. Methods by which to address these situations are examined. It has been shown that synergy between the spectroscopist and the expert system allows the solution of problems that seemed to be hopeless at the outset of the structure elucidation process.
Reactions of nitroarenes with secondary and tertiary carbanions bearing both a leaving group and electron‐withdrawing group: An approach to dihydronaphth[2,1‐c]isoxazole N‐oxides and dihydroisoxazolo[4,3‐f]quinoline N‐oxides
Authors: Maruoka Hiroshi , Tomioka Yukihiko
Published: April 2009

2‐Nitronaphthalene (1) and 6‐nitroquinoline (2) underwent direct cyclocondensation with secondary and tertiary carbanions derived from a methylene and methine group bearing both a leaving group and electron‐withdrawing group (e.g., methyl chloroacetate, ethyl chloroacetate, chloroacetonitrile, methyl 2‐chloropropionate, ethyl 2‐chloropropionate and 2‐chloropropionitrile) in the sodium hydride/N,N‐dimethylformamide system at low temperature, giving the corresponding dihydronaphth[2,1‐c]isoxazole N‐oxides 3 and dihy‐droisoxazolo[4,3‐f]quinoline N‐oxides 4. On the other hand, nitroarenes 1 and 2 reacted with secondary carbanions in the sodium hydride/tetrahydrofuran system to yield the corresponding conventional vicarious nucleophilic substitution (VNS) products 5 and 6.
Reactions of 4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines with α,β‐unsaturated carbonyl compounds
Authors: Lipson Victoria V. , Ignatenko Irina V. , Desenko Sergey M. , Shishkina Svetlana V. , Shishkin Oleg V. , Komykhov Sergey A. , Logvinenko Natalya V. , Orlov Valery D. , Meier Herbert
Published: April 2009

The reaction of 5,7‐diphenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine (1) with α,β‐unsaturated carbonyl compounds 2a‐f led to the formation of the alkylated heterocycles 3a‐f (Figure 1). However, the reaction of 5‐methyl‐7‐phenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine (5) with 2a‐c yielded under the same conditions the triazolo[5,1‐b]quinazolines 6a‐c (Figure 3). In this case, the alkylation is followed by a cyclocondensation. The structure elucidation of the products is based on ir, ms, 1H and 13C nmr measurements and on an X‐ray diffraction study.
Synthesis of pyrimido[1,2‐a]benzimidazol‐4(10H)‐one derivatives and evaluation of their interactions with DNA
Authors: Da Settimo A. , Primofiore G. , Da Settimo F. , Marini A. M. , Taliani S. , Salerno S. , Dalla Via L.
Published: April 2009

The synthesis of new derivatives of the planar tricyclic pyrimido[1,2‐a]benzimidazole system featuring protonable side chains in the 3 and/or 10 positions is described. The reported literature procedures for the preparation of the intermediate 3‐ethoxycarbonylpyrimido[1,2‐a]benzimidazol‐4(10H)‐one 15, starting from 2‐aminobenzimidazole 18 and diethyl ethoxymethylenemalonate, were revised. The interaction with DNA, the intrinsic binding constants, and the antiproliferative activity of a number of compounds (1–8, 10, 11) were preliminarly investigated.
Structural investigation of 3,5‐disubstituted isoxazoles by 1H‐nuclear magnetic resonance
Authors: Sechi Mario , Sannia Luciano , Orecchioni Maria , Carta Fabrizio , Paglietti Giuseppe , Neamati Nouri
Published: April 2009

HIV‐1 integrase (IN) is a very promising and validated target for the development of therapeutic agents against AIDS. In an effort to design and synthesize biological isosteric analogs of β‐diketoacid‐containing inhibitors of IN, we prepared a series of substituted isoxazole carboxylic acids. Several of these compounds inhibited catalytic activities of purified IN at micromolar concentration range. With an aim to prepare a large number of analogues based on the isoxazole pharmacophore we focused our study on a series of 3,5‐disubstituted isoxazole isomers. For a rapid structural analysis we discovered a convenient 1H‐nmr method for distinguishing between isomeric structures based on their H‐4 assignments. This “finger print” approach to isomer identification will be useful in combinatorial chemistry settings where a mixture can be further derivatized.