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Open AccessEditorial

Biologically Relevant Heterocyclic Compounds

by Lucjan Strekowski

Molecules 2004, 9(3), 39; https://doi.org/10.3390/90300039 - 28 Feb 2004

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Abstract

Heterocyclic chemistry is a rapidly growing branch of organic chemistry. [...] Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

Research

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170 KiB

Open AccessArticle

Biaryl Product Formation from Cross-coupling in Palladiumcatalyzed Borylation of a Boc Protected Aminobromoquinoline Compound

by Hao Fang, Jun Yan and Binghe Wang

Molecules 2004, 9(3), 178-184; https://doi.org/10.3390/90300178 - 28 Feb 2004

Cited by 14 | Viewed by 10967

Abstract

The palladium catalyzed borylation of a Boc protected aminobromoquinoline compound with bis(pinacolato)diboron yielded a biaryl compound, resulting from cross coupling, as the major product, instead of the intended boronate, even though no strong base was used. Such results indicate that under certain conditions [...] Read more.

The palladium catalyzed borylation of a Boc protected aminobromoquinoline compound with bis(pinacolato)diboron yielded a biaryl compound, resulting from cross coupling, as the major product, instead of the intended boronate, even though no strong base was used. Such results indicate that under certain conditions and with certain substrates, cross coupling can be a major problem during borylation, leading to unintended consequences. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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211 KiB

Open AccessArticle

New Imide 5-HT1A Receptor Ligands – Modification of Terminal Fragment Geometry

by Andrzej J. Bojarski, Maria J. Mokrosz, Beata Duszyńska, Aneta Kozioł and Ryszard Bugno

Molecules 2004, 9(3), 170-177; https://doi.org/10.3390/90300170 - 28 Feb 2004

Cited by 18 | Viewed by 10049

Abstract

Two sets of new o-methoxyphenylpiperazine (MPP; series a) and 1,2,3,4-tetrahydroisoquinoline (THIQ; series b) derivatives, containing various imide moietiesderived from NAN190, were synthesized and evaluated in vitro for their ability to bind tothe serotonin 5-HT_1A and 5-HT_2A receptors. All new derivatives from [...] Read more.

Two sets of new o-methoxyphenylpiperazine (MPP; series a) and 1,2,3,4-tetrahydroisoquinoline (THIQ; series b) derivatives, containing various imide moietiesderived from NAN190, were synthesized and evaluated in vitro for their ability to bind tothe serotonin 5-HT_1A and 5-HT_2A receptors. All new derivatives from series a demonstratedhigh 5-HT_1A affinities, whereas THIQ analogues were much less active. With respect to5-HT_2Areceptors, three MPP derivatives presented moderate activity but the rest of theinvestigated compounds were practically inactive. The influence of changes in terminusgeometry on 5-HT_1A receptor affinity was analyzed in regard to model compounds NAN190and MM199. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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101 KiB

Open AccessArticle

Phenoxydifluoromethyl Substituted Nitrogen Heterocycles. Synthesis and Heterocyclization Reactions of Ethyl 4,4-Difluoro- 4-phenoxyacetoacetate

by S. Yu. Solodukhin, A. S. Peregudov, E. V. Vorontsov and N. D. Chkanikov

Molecules 2004, 9(3), 164-169; https://doi.org/10.3390/90300164 - 28 Feb 2004

Cited by 4 | Viewed by 8624

Abstract

Ethyl 4,4-difluoro-4-phenoxyacetoacetate was obtained and studied as a precursor to new heterocyclic compounds. 6-Hydroxypyrimidine, 1,3-dihydro-1,5- benzodiazepin-2-one, quinolin-2-one and 6-hydroxypyrazolo[3,4-b]pyridine derivatives containing phenoxydifluoromethyl groups were synthesized. These results make it possible to introduce aryloxydifluoromethyl substituents for the design of biologically active heterocycles. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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165 KiB

Open AccessArticle

The Synthesis of Dicationic Extended Bis-Benzimidazoles

by Zhijan Kang, Christine C. Dykstra and David W. Boykin

Molecules 2004, 9(3), 158-163; https://doi.org/10.3390/90300158 - 28 Feb 2004

Cited by 9 | Viewed by 8441

Abstract

The synthesis of extended dicationic bis-benzimidazoles starting from trans-1,2-bis(4-cyanophenyl)ethene and trans-1,2-bis(4-cyanophenyl)cyclopropane is reported. The target diamidines show significant in vitro activity against B. subtilis. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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246 KiB

Open AccessArticle

Lipid-Lowering Effects of Ethyl 2-Phenacyl-3-aryl-1H-pyrrole- 4-carboxylates in Rodents

by Justin M. Holub, Kathy O'Toole-Colin, Adam Getzel, Anthony Argenti, Michael A. Evans, Daniel C. Smith, Gerard A. Dalglish, Shahzad Rifat, Donna L. Wilson, Brett M. Taylor, Ulander Miott, Josephine Glersaye, Kam Suet Lam, Bryan J. McCranor, Joshua D. Berkowitz, Robert B. Miller, John R. Lukens, Keith Krumpe, John T. Gupton and Bruce S. Burnham

Molecules 2004, 9(3), 134-157; https://doi.org/10.3390/90300134 - 28 Feb 2004

Cited by 34 | Viewed by 14187

Abstract

A series of substituted 2-phenacyl-3-phenyl-1H-pyrrole-4-carboxylates were prepared from substituted acetophenones in 6 steps. The final condensations between a chloroenal and an aminoketone were carried out under neutral conditions in parallel to yield the series listed below. Selected pyrrole derivatives proved to be potent [...] Read more.

A series of substituted 2-phenacyl-3-phenyl-1H-pyrrole-4-carboxylates were prepared from substituted acetophenones in 6 steps. The final condensations between a chloroenal and an aminoketone were carried out under neutral conditions in parallel to yield the series listed below. Selected pyrrole derivatives proved to be potent hypolipidemic agents lowering serum triglyceride concentrations in CF-1 male mice after 14 days of I.P. administration. One agent orally lowered serum cholesterol in Sprague-Dawley male rats at 2mg/kg/day after 14 days. The agents demonstrated a lowering of mouse serum LDL- cholesterol levels and selected compounds showed an elevation of serum HDL-cholesterol levels. The cholesterol concentrations in the liver were raised while the cholesterol and triglyceride contents of the aorta were significantly lowered by the selected trisubstituted pyrrole. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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223 KiB

Open AccessArticle

Unexpected Syntheses of seco-Cyclopropyltetrahydroquinolines >From a Radical 5-Exo-Trig Cyclization Reaction: Analogs of CC-1065 and the Duocarmycins

by Hari Pati, Lori Forrest, Heather Townes, Brian Lingerfelt, LuAnne McNulty and Moses Lee

Molecules 2004, 9(3), 125-133; https://doi.org/10.3390/90300125 - 28 Feb 2004

Cited by 8 | Viewed by 10306

Abstract

Analogs of the seco-cyclopyrroloindoline (seco-CPI), the DNA alkylation pharmacophore of CC-1065 and the duocarmycins, can be prepared through a 5-exo-trig radical cyclization of a free radical and a 3-chloro-2-allylic moiety. This manuscript reports an unexpected discovery that, depending on the structure and stability [...] Read more.

Analogs of the seco-cyclopyrroloindoline (seco-CPI), the DNA alkylation pharmacophore of CC-1065 and the duocarmycins, can be prepared through a 5-exo-trig radical cyclization of a free radical and a 3-chloro-2-allylic moiety. This manuscript reports an unexpected discovery that, depending on the structure and stability of the free radical, the cyclization process leads to the production of an appreciable amount of seco- cyclopropyltetrahydroquinolines 7a-d along with the seco-cyclopropoyltetra- hydroindoline products (6a-e). For instance, free radical reaction of the bromoallylic chloride 5a produced an equal amount of 6-benzyloxy-N-t-butoxycarbonyl-3- (chloromethyl)furano[e]indoline (6a), and 7-benzyloxy-N-t-butoxycarbonyl-3-chloro- 1,2,3,4-tetrahydrofurano[f]quinoline (7a). Three other examples that produced mixtures of indoline and quinoline products are provided. In only one of the examples reported in this manuscript, the 6-benzyloxy-N-t-butoxycarbonyl-3-(chloromethyl)benzo[e]indoline, was a seco-CBI precursor 6e formed exclusively, consistent with literature precedents. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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159 KiB

Open AccessArticle

Kinetics of the Epoxidation of Geraniol and Model Systems by Dimethyldioxirane

by A. L. Baumstark, P. J. Franklin, P. C. Vasquez and B. S. Crow

Molecules 2004, 9(3), 117-124; https://doi.org/10.3390/90300117 - 28 Feb 2004

Cited by 11 | Viewed by 9596

Abstract

The mono-epoxidation of geraniol by dimethyldioxirane was carried out invarious solvents. In all cases, the product ratios for the 2,3 and 6,7 mono-epoxides werein agreement with literature values. Kinetic studies were carried out at 23 ^oC in thefollowing dried solvent systems: acetone [...] Read more.

The mono-epoxidation of geraniol by dimethyldioxirane was carried out invarious solvents. In all cases, the product ratios for the 2,3 and 6,7 mono-epoxides werein agreement with literature values. Kinetic studies were carried out at 23 ^oC in thefollowing dried solvent systems: acetone (k₂ = 1.49 M^-1s^-1), carbon tetrachloride/acetone(9/1, k₂=2.19 M^-1s^-1), and methanol/acetone (9/1, k₂ = 17 M^-1s^-1). Individual k₂ valueswere calculated for epoxidation of the 2,3 and 6,7 positions in geraniol. The non-conjugated diene system was modeled employing two simple independent alkenes:2-methyl-2-pentene and 3-methyl-2-buten-1-ol by determining the respective k₂ valuesfor epoxidation in various solvents. The kinetic results for each independent alkeneshowed that the relative reactivity of the two epoxidation sites in geraniol as a function ofsolvent was not simply a summation of the independent alkene systems. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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169 KiB

Open AccessArticle

Synthesis and Antitumor Activity of 5-Trifluoromethyl-2,4- dihydropyrazol-3-one Nucleosides

by Ibrahim M. Abdou, Ayman M. Saleh and Hussein F.. Zohdi

Molecules 2004, 9(3), 109-116; https://doi.org/10.3390/90300109 - 28 Feb 2004

Cited by 80 | Viewed by 10981

Abstract

2,4-Dihydropyrazole glucosides 3a-3c were prepared and tested for theirantitumor activity. The structures of these compounds were established by ¹H and ¹³C-NMR spectroscopy. Glucoside 3b shows an in vitro IC₅₀ value of 16.4 μM againstproliferation of the human promyelotic leukemia (HL60) cell line. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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159 KiB

Open AccessArticle

Structure-Activity Relationships for the 9-(Pyridin-2’-yl)- aminoacridines

by Michael D. Mosher, Kristi L. Holmes and Katherine S. Frost

Molecules 2004, 9(3), 102-108; https://doi.org/10.3390/90300102 - 28 Feb 2004

Cited by 5 | Viewed by 8272

Abstract

A series of 9-(pyridin-2’-yl)-aminoacridines was prepared and analyzed for their ability to change the thermal denaturation temperature of genomic calf thymus DNA. Development of a QSAR equation indicated that electron withdrawing groups on the pyridine ring promoted the interaction with double stranded DNA. [...] Read more.

A series of 9-(pyridin-2’-yl)-aminoacridines was prepared and analyzed for their ability to change the thermal denaturation temperature of genomic calf thymus DNA. Development of a QSAR equation indicated that electron withdrawing groups on the pyridine ring promoted the interaction with double stranded DNA. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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359 KiB

Open AccessArticle

Synthesis, Molecular Structure and Reactivity of 5-Methylidene-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolines

by Anita Kornicka, Franciszek Sączewski and Maria Gdaniec

Molecules 2004, 9(3), 86-101; https://doi.org/10.3390/90300086 - 28 Feb 2004

Cited by 12 | Viewed by 10737

Abstract

Synthesis of novel 5-methylidene-1,2,3,5-tetrahydro[2,1-b]-quinazolinederivatives 2-4 with potential biological activities mediated by α-adrenergic and/orimidazoline receptors was performed by reacting 2-chloro-4,5-dihydroimidazole (1) withthe corresponding 2-aminoacetophenones. Compound 2, which incorporates an enaminemoiety, underwent a 1,3-dipolar cycloaddition reaction with the appropriate nitrones 5-9to give 1,2,3,5-tetrahydro-imidazo[2,1-b]quinazolin-5,5'-spiro-2',3'-diphenylisoxazol-idines 10-14. Reactions [...] Read more.

Synthesis of novel 5-methylidene-1,2,3,5-tetrahydro[2,1-b]-quinazolinederivatives 2-4 with potential biological activities mediated by α-adrenergic and/orimidazoline receptors was performed by reacting 2-chloro-4,5-dihydroimidazole (1) withthe corresponding 2-aminoacetophenones. Compound 2, which incorporates an enaminemoiety, underwent a 1,3-dipolar cycloaddition reaction with the appropriate nitrones 5-9to give 1,2,3,5-tetrahydro-imidazo[2,1-b]quinazolin-5,5'-spiro-2',3'-diphenylisoxazol-idines 10-14. Reactions of the title compounds 2 and 4 with dimethyl acetylene-dicarboxylate (DMAD) afforded dimethyl 2-(2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ylidenemethyl)but-2-enedioates 15, 16. Imidazo[2,1-b]quinazoline 2 was furthertreated with acetyl chloride, benzoyl chloride and mesyl chloride to give the 1-substitutedderivatives 17, 18 and 19, respectively. The structures of all new compounds obtainedwere confirmed by elemental analysis and spectral data (IR, ¹H- and ¹³C-NMR) as well asX-ray crystallographic analysis of 3 and 18. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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309 KiB

Open AccessArticle

Probing the Structure of DNA Aptamers with a Classic Heterocycle.

by Arthur E. Wood IV and G. Reid Bishop

Molecules 2004, 9(3), 67-85; https://doi.org/10.3390/90300067 - 28 Feb 2004

Cited by 7 | Viewed by 10064

Abstract

DNA aptamers are synthetic, single-stranded DNA oligonucleotides selectedby SELEX methods for their binding with specific ligands. Here we present ethidiumbinding results for three related DNA aptamers (PDB code: 1OLD, 1DB6, and 2ARG)that bind L-argininamide (L-Arm). The ligand bound form of each aptamer's structurehas [...] Read more.

DNA aptamers are synthetic, single-stranded DNA oligonucleotides selectedby SELEX methods for their binding with specific ligands. Here we present ethidiumbinding results for three related DNA aptamers (PDB code: 1OLD, 1DB6, and 2ARG)that bind L-argininamide (L-Arm). The ligand bound form of each aptamer's structurehas been reported and each are found to be composed primarily of two domainsconsisting of a stem helical region and a loop domain that forms a binding pocket for thecognate ligand. Previous thermodynamic experiments demonstrated that the DNAaptamer 1OLD undergoes a large conformational ordering upon binding to L-Arm. Herewe extend those linkage binding studies by examining the binding of the heterocyclicintercalator ethidium to each of the three aptamers by fluorescence and absorptionspectrophotometric titrations. Our results reveal that ethidium binds to each aptamer with∆G^o's in the range of -8.7 to -9.4 kcal/mol. The stoichiometry of binding is 2:1 for eachaptamer and is quantitatively diminished in the presence of L-Arm as is the overallfluorescence intensity of ethidium. Together, these results demonstrate that a portion ofthe bound ethidium is excluded from the aptamer in the presence of a saturating amountof L-Arm. These results demonstrate the utility of ethidium and related compounds forthe probing of non-conventional DNA structures and reveal an interesting fundamentalthermodynamic linkage in DNA aptamers. Results are discussed in the context of thethermodynamic stability and structure of each of the aptamers examined. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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Review

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237 KiB

Open AccessReview

New Synthetic Routes to Furocoumarins and Their Analogs: A Review

by Valery F. Traven

Molecules 2004, 9(3), 50-66; https://doi.org/10.3390/90300050 - 28 Feb 2004

Cited by 38 | Viewed by 12564

Abstract

Many furocoumarins and their analogs possess a prominent photobiological activity. Some of them are successfully used as drugs in phototherapy of skin diseases. Fries rearrangement of acyloxyheteroarenes, condensation of acylhydroxyheteroarenes with α-carbonyl compounds under base catalysis and transformations of dihydrofurocoumarinones are new trends [...] Read more.

Many furocoumarins and their analogs possess a prominent photobiological activity. Some of them are successfully used as drugs in phototherapy of skin diseases. Fries rearrangement of acyloxyheteroarenes, condensation of acylhydroxyheteroarenes with α-carbonyl compounds under base catalysis and transformations of dihydrofurocoumarinones are new trends in synthesis of furocoumarins and their analogs. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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1854 KiB

Open AccessReview

Noncovalent Labeling of Biomolecules with Red and Near- Infrared Dyes

by Gabor Patonay, Jozef Salon, John Sowell and Lucjan Strekowski

Molecules 2004, 9(3), 40-49; https://doi.org/10.3390/90300040 - 28 Feb 2004

Cited by 145 | Viewed by 16297

Abstract

Biopolymers such as proteins and nucleic acids can be labeled with a fluorescent marker to allow for their detection. Covalent labeling is achieved by the reaction of an appropriately functionalized dye marker with a reactive group on a biomolecule. The recent trend, however, [...] Read more.

Biopolymers such as proteins and nucleic acids can be labeled with a fluorescent marker to allow for their detection. Covalent labeling is achieved by the reaction of an appropriately functionalized dye marker with a reactive group on a biomolecule. The recent trend, however, is the use of noncovalent labeling that results from strong hydrophobic and/or ionic interactions between the marker and biomolecule of interest. The main advantage of noncovalent labeling is that it affects the functional activity of the biomolecule to a lesser extent. The applications of luminescent cyanine and squarylium dyes are reviewed. Full article

(This article belongs to the Special Issue Biologically Relevant Heterocyclic Compounds)

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