Showing papers on "Bicyclic molecule published in 2002"

Pyrido [2, 3‐d]pyrimidines and Pyrimido[5′, 4′:5, 6]pyrido[2, 3‐d]pyrimidines as New Antiviral Agents: Synthesis and Biological Activity

Abstract: A series of 7-amino- and 7-oxo-5-aryl-6-cyanopyrido[2, 3-d]pyrimidines, 4 and 11, respectively, and pyrimido [5', 4':5, 6]pyrido[2, 3-d]pyrimidine derivatives 6 and 7 was synthesized and investigated as antiviral agents. Different synthetic strategies for the preparation of the target compounds were explored. A synthetic procedure for 4 and 11 starting with 6-amino-1, 2, 3, 4-tetrahydro-2, 4-dioxopyrimidine, proper aldehyde, and malononitrile or ethyl cyanoacetate, respectively, in a one-pot reaction proved to be the method of choice for preparation of compounds of such type. Construction of another pyrimidine ring on the pyridine nucleus of compound 4 was achieved either by reaction with phenyl iso(thio)cyanate or with formic acid to yield 6 and 7, respectively. The structure of the prepared compounds was confirmed through elemental analysis and spectral investigation. Most of the newly synthesized compounds were subjected to antiviral activity testing against herpes simplex virus (HSV) where some of them show good activities.

Synthesis and antiviral activity evaluation of some new 6-substituted 3-(1-adamantyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles.

Abstract: A number of novel 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives, containing the adamantyl moiety, were synthesized and examined in various viral test systems No antiviral effects were noted with any of the compounds at subtoxic concentrations in cell culture

Carbopalladation of Nitriles: Synthesis of 2,3-Diarylindenones and Polycyclic Aromatic Ketones by the Pd-Catalyzed Annulation of Alkynes and Bicyclic Alkenes by 2-Iodoarenenitriles

Abstract: 2-Iodobenzonitrile, its derivatives, and various heterocyclic analogues undergo palladium(0)-catalyzed annulation onto diarylacetylenes or bicyclic alkenes to afford 2,3-diarylindenones and polycyclic aromatic ketones in very good to excellent yields. This reaction represents one of the first examples of the addition of an organopalladium moiety to the carbon−nitrogen triple bond of a nitrile. The reaction is compatible with a number of functional groups. A reaction mechanism, as well as a model accounting for the electronic effects of substituents on the aromatic ring of the nitrile, is proposed.

2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer

Abstract: A coumpound of the formula (I) wherein each X is independently NR1R6, NR4R5, or R4, with the proviso that at least one X must be NR1R6; each R1 is independently an optionally substituted fused bicyclic unsaturated ring containing 9 or 10 atoms optionally containing 1-4 heteroatoms selected from the group consisting of N, S and O, and the variables R2-6 are as defined in claim 1, are claimed. These compounds are kinase inhibitors useful in the treatment of cancer and viral infections.

Thieno[3,4-b]pyrazines: Synthesis, Structure, and Reactivity

Abstract: A general synthetic route has been developed for the efficient preparation of 2,3-disubstituted thieno[3,4-b]pyrazines These methods eliminate problems in the preparation of the precursor 3,4-diaminothiophene and utilize α-diones prepared through the reaction of the appropriate organocuprates with oxalyl chloride This combination allows the convenient preparation of thieno[3,4-b]pyrazine and its 2,3-disubstituted analogues (where substituent = methyl, hexyl, octyl, decyl, dodecyl, and phenyl) in high yield Characterization of the structure and reactivity of this class of compounds is also described, including the results of structural, electrochemical, and pKa studies

Three-Component Cycloadditions: The First Transition Metal-Catalyzed [5+2+1] Cycloaddition Reactions

Abstract: Prompted by our studies of transition metal-catalyzed [4+4], [4+2], [5+2], and [6+2] cycloadditions and by the view that these two-component reactions could be intercepted by a third component of one or more atoms, a new three-component transition metal-catalyzed cycloaddition is described. This new [5+2+1] cycloaddition proceeds in good to excellent yield and with high or complete regioselectivity with a variety of carbonyl-substituted alkynes to give bicyclo[3.3.0]octenone adducts, resulting from transannular closure of the intermediate eight-membered-ring cycloadduct. Effects of concentration, temperature, pressure, and catalyst loading on the efficiency of the reaction are discussed. This process provides access to complex building blocks for synthesis based on simple, readily available components.

Synthesis of Cyclical Diamine Templated Uranium Sulfates

Abstract: The hydrothermal synthesis of uranium sulfates in the presence of a series of structurally related organic templating agents has been investigated. Piperazine, 2-methylpiperazine, and 1,4-diazabicyclo[2.2.2]octane, each of which is based upon the same six-membered cyclical diamine, exhibit different point symmetries and hydrogen-bonding characteristics. Small changes in the template structure result in marked differences in the reaction product. Three new compounds were synthesized and structurally characterized, [N2C4H12][UO2(H2O)(SO4)2], [N2C5H14][UO2(H2O)(SO4)2], and [N2C6H14][UO2(H2O)(SO4)2]. The inorganic framework of each compound was found to be dependent on the template structure. [N2C4H12][UO2(H2O)(SO4)2] consists of one-dimensional [UO2(H2O)(SO4)4/2]∞2- chains, which hydrogen bond to one another to form quasi two-dimensional layers. One-dimensional chains are observed in [N2C5H14][UO2(H2O)(SO4)2]. These chains, which have the formula [UO2(H2O)(SO4)4/2(UO2(H2O)(SO4)2)]∞4- are unprecedented in ura...

Highly Stereoselective Asymmetric 6π-Azaelectrocyclization Utilizing the Novel 7-Alkyl Substituted cis-1-Amino-2-indanols: Formal Synthesis of 20-Epiuleine

Abstract: Highly stereoselective asymmetric 6π-azaelectrocyclization was achieved with generality, based on the reaction between the (E)-3-carbonyl-2,4,6-trienal compounds and the (−)-7-alkyl-cis-1-amino-2-indanol derivatives as the effective novel chiral amines. Furthermore, the chiral auxiliaries of the cyclized products obtained were efficiently removed by the novel manganese dioxide oxidation under remarkably mild conditions, and the method was successfully applied to the formal synthesis of optically active 20-epiuleine.

Nucleosides having bicyclic sugar moiety

Abstract: Conformationally restricted 2′, 4′-bridged nucleoside analogues are described herein. The compounds can be prepared by cyclization at C2′ and C4′ of nucleosides through a linker or linking molecule. These novel nucleosides have a desired, locked sugar pucker and are potentially useful as pharmaceutical ingredients, and especially for use in treatment of HCV.

Structure-affinity relationship study on N-[4-(4-arylpiperazin-1-yl)butyl]arylcarboxamides as potent and selective dopamine D3 receptor ligands

Abstract: The benzamide PB12 (N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide) (1), already reported as potent and selective dopamine D(4) receptor ligand, has been modified searching for structural features that could lead to D(3) receptor affinity. Changes in the aromatic ring linked to N-1 piperazine ring led to the identification of 2-methoxyphenyl and 2,3-dichlorophenyl derivatives (compounds 6 and 13) displaying moderate D(3) affinity (K(i) = 145 and 31 nM, respectively). Intermediate alkyl chain elongation in compounds 1, 6, and 13 improved binding affinity for the D(3) receptor and decreased the D(4) affinity (compounds 18-26). Among these latter compounds, the N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-3-methoxybenzamide (19) was further modified with the replacement or of the 2,3-dichlorophenyl moiety (compounds 27-30) or of the 3-methoxyphenyl ring (compounds 31-41). In this way, we identified several high-affinity D(3) ligands (0.13 nM < K(i)'s < 4.97 nM) endowed with high selectivity over D(2), D(4), 5-HT(1A), and alpha(1) receptors. In addition, N-[4-[4-(2,3-dimethylphenyl)piperazin-1-yl]butyl]-3-methoxybenzamide (27) and N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofurancarboxamide (41) appear to be valuable candidates for positron emission tomography (PET) because of their affinity values, lipophilicity properties, and liability of (11)C labeling in the O-methyl position.

Novel structures derived from 2-[[(2-pyridyl)methyl]thio]-1H-benzimidazole as anti-Helicobacter pylori agents, Part 1.

Abstract: 2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazoles (2, sulfides) exhibit antibacterial properties that are selective for Helicobacter spp., but they also have an inherent susceptibility to metabolic oxidation to furnish 2-[[(2-pyridyl)methyl]sulfinyl]-1H-benzimidazoles (1), which act as proton pump inhibitors (PPIs). We have discovered five compounds with retained antibacterial potency and selectivity in which the overall framework of the sulfides 2 could be kept intact while structural modifications were made to remove PPI activity. These compounds, 2-[((2-methyl-3-(2-(2-(2-methoxyethoxy)ethoxy)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (79), 2-[((2-methyl-3-(2-(2-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)ethoxy)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (80), 2-[((2-methyl-3-((2-morpholino)ethylthio)phenyl)methyl)thio]-1H-benzimidazole (86), 2-[[[2-methyl-3-[2-(2-methyl-5-nitroimidazol-1-yl)ethylthio]phenyl]methyl]thio]-1H-benzimidazole (88), and 2-[[[2-methyl-3-[2-(1,2,4-triazol-1-yl)ethylthio]phenyl]methyl]thio]-1H-benzimidazole (89), had minimum bactericidal concentrations (MBCs) of 0.5, 0.5, 1, 2, and 4 microg/mL, respectively. The reported compounds are bactericidal with MBCs within 1 order of magnitude of MBCs of clinically used antimicrobials such as clarithromycin (0.1 microg/mL) or metronidazole (2-4 microg/mL) but differ from these inasmuch that they have an extremely narrow spectrum activity and appear to be species specific.

Intermolecular transition metal-catalyzed [4 + 2 + 2] cycloaddition reactions: A new approach to the construction of eight-membered rings

Abstract: Transition metal-catalyzed cycloaddition reactions represent powerful methods for the construction of complex polycyclic systems. We have developed a new intermolecular metal-catalyzed [4 + 2 + 2] cycloaddition of heteroatom-tethered enyne derivatives with 1,3-butadiene. This study demonstrates that excellent selectivity can be obtained for the heterocycloaddition adducts through the judicious choice of silver salt. The development of the tandem rhodium-catalyzed allylic substitution [4 + 2 + 2] cycloaddition provides a convenient three-component coupling that circumvents the prior formation of the enyne derivative. Finally, the introduction of a stereogenic center at C-2 leads to a diastereoselective cycloaddition, which provides a powerful new method for the construction of bicyclic octanoid ring systems applicable to target directed synthesis.

Intramolecular hydrogen abstraction reaction promoted by alkoxy radicals in carbohydrates. Synthesis of chiral 2,7-dioxabicyclo[2.2.1]heptane and 6,8-dioxabicyclo[3.2.1]octane ring systems.

Abstract: The reaction of specifically protected anhydroalditols with (diacetoxyiodo)benzene or iodosylbenzene and iodine is a mild and selective procedure for the synthesis of chiral 6,8-dioxabicyclo[3.2.1]octane and 2,7-dioxabicyclo[2.2.1]heptane ring systems under neutral conditions. This reaction can be considered to be an intramolecular glycosidation that goes through an intramolecular hydrogen abstraction promoted by an alkoxy radical followed by oxidation of the transient C-radical intermediate to an oxycarbenium ion. This methodology is useful not only for the preparation of chiral synthons but also for the selective oxidation of specific carbons of the carbohydrate skeleton, constituting a good procedure for the synthesis of protected uloses.

Ruthenium-catalyzed cycloaddition of 1,6-diynes with isothiocyanates and carbon disulfide: first transition-metal catalyzed [2 + 2 + 2] cocyclotrimerization involving C=S double bond.

Abstract: In the presence of 10 mol % Cp*Ru(cod)Cl, 1,6-diynes with a tertiary center at 4-position reacted with various isothiocyanates at their CS double bond to afford bicyclic (2H)-thiopyranimines in 35−88% yields. The (2H)-thiopyran structure was unequivocally determined by X-ray analysis. The cycloaddition of carbon disulfide with a diyne similarly gave the expected bicyclic dithiopyrone in 50% yield.

Traceless solid-phase synthesis of bicyclic dihydropyrimidones using multidirectional cyclization cleavage.

Abstract: Solid-phase and solution-phase protocols for the synthesis of furo[3,4-d]pyrimidines, pyrrolo[3,4-d]pyrimidines, and pyrimido[4,5-d]pyridazines are reported. The multistep solid-phase sequence involves the initial high-speed, microwave-promoted acetoacetylation of hydroxymethylpolystyrene resin with methyl 4-chloroacetoacetate. The immobilized 4-chloroacetoacetate precursor was subsequently subjected to three-component Biginelli-type condensations employing urea and a variety of aromatic aldehydes. The resulting 6-chloromethyl-functionalized resin-bound dihydropyrimidones served as common chemical platforms for the generation of the desired heterobicyclic scaffolds using three different traceless cyclative cleavage strategies. The corresponding furo[3,4-d]pyrimidines were obtained by microwave flash heating in a rapid, thermally triggered, cyclative release. Treatment of the chloromethyl dihydropyrimidone intermediates with a variety of primary amines followed by high-temperature microwave heating furnish...

Homochiral Metal−Organic Frameworks Based on Transition Metal Bisphosphonates

Abstract: Homochiral metal−organic frameworks with binaphthylbisphosphonate bridging ligands [Mn(L-H2)(MeOH)]·(MeOH), 1, [Co2(L-H2)2(H2O)3]·(H2O)4, 2, [Ni(L-H2)(MeOH)4], 3, [Cu(L-Et2)], 4, and [Zn3(L-H)2(C6H5N)2], 5, where L is completely deprotonated enantiopure 2,2‘-diethoxy-1,1‘-binaphthalene-6,6‘-bisphosphonic acid, were synthesized under hydro(solvo)thermal reactions. Single-crystal X-ray diffraction studies reveal that 3−5 adopt condensed network structures, while compounds 1 and 2 adopt robust three-dimensional open-framework structures possessing rhombohedral channels. Solid-state circular dichroism spectra indicate that compounds 1−5 made from bridging ligands of opposite handness are supramolecular enantiomers. Compounds 1, 5, and L-H4 exhibit strong blue fluorescence in solid state, and the formation of excimers in 5 and L-H4 in solid state correlates well with the π−π stacking interactions. The present work illustrates the potential of rational synthesis of robust chiral porous network solids. The chira...

Pyrimidine a2b selective antagonist compounds, their synthesis and use

Abstract: The subject invention provides compounds having the structure:, wherein R1 is substituted or unsubstituted phenyl or a 5-6 membered heterocyclic or heteroaromatic ring containing from 1 to 5 heteroatoms; R2 is hydrogen, or a substituted or unsubstituted alkyl, -C(O)-alkyl, -C(O)-O-alkyl, alkoxy, cycloalkyl, alkenyl, monocyclic or bicyclic aryl, heteroaryl or heterocyclic moiety; R3 is hydrogen, or a substituted or unsubstituted alkyl, -C(O)-alkyl, -C(O)-O-alkyl, alkoxy, cycloalkyl, alkenyl, monocyclic or bicyclic aryl, heteroaryl or heterocyclic moiety, or R2 and R3 are joined to form a heterocyclic ring; wherein the dashed line represents a second bond which may be present or absent, and when present R3 is oxygen; R4 and R5 are each independently substituted or unsubstituted alkyl, -C(O)-alkyl, -C(O)-O-alkyl, alkoxy, cycloalkyl, alkenyl, monocyclic or bicyclic aryl, heteroaryl or heterocyclic moiety, or R4NR5 together form a substituted or unsubstituted monocyclic or bicyclic, heterocyclic or heteroaryl moiety containing from 1 to 6 heteroatoms; R12 is hydrogen, alkyl, halogen or cyano; and n is 0, 1, 2, 3 or 4, or an enantiomer, or a specific tautomer, or a pharmaceutically acceptable salt thereof and a method for treating a disease associated with the A2b adenosine receptor by administering a therapeutically effective amount of the compounds of the invention.

Reversal of enantioselectivity in the asymmetric rhodium- versus iridium-catalyzed hydroboration of meso substrates.

Abstract: The Ir-catalyzed asymmetric hydroboration of bicyclic hydrazines with ee and chemical yields up to 64% is reported. The switch from rhodium to iridium leads systematically to opposite enantiomers in this desymmetrization reaction.

Catalytic enantioselective 1,3-dipolar cycloaddition of nitrones to cyclopent-1-enecarbaldehyde

Abstract: A variety of pyrrolidinium salts have been found to catalyse the reaction between nitrones and a cyclic α,β-unsaturated aldehyde furnishing bicyclic adducts with high diastereoselectivity and enantioselectivity.

Formation of isoprostane bicyclic endoperoxides from the autoxidation of cholesteryl arachidonate.

Abstract: Autoxidation of polyunsaturated fatty acids and esters leads to a complex mixture containing hydroperoxides and cyclic peroxides. Prostaglandin bicyclic endoperoxides have been detected from the autoxidation of cholesteryl arachidonate by LC-MS and GC-MS techniques. All four possible types (I-IV) of bicyclic endoperoxides have been found starting from different regioisomeric hydroperoxides of cholesteryl arachidonate. Furthermore, the stereochemistry of Type IV bicyclic endoperoxides has been determined by conversion to pentafluorobenzyl (PFB) ester, trimethylsilyl (TMS) derivatives, and comparison with synthetic standards by the use of GC-MS. All eight possible diastereomers of the derivatized isoprostanes were observed and were separated by gas chromatography. The bicyclic endoperoxides with the two alkyl chains syn on the cyclopentane ring were formed preferentially to those with anti configuration, a result anticipated from earlier work. Substantial amounts of the anti-substituted isoprostanes, including PGF(2)(alpha), were, however, observed in the product mixture.

Selective preparation of benzyltitanium compounds by the metalative Reppe reaction. Its application to the first synthesis of alcyopterosin A.

Abstract: Dialkoxytitanacyclopentadienes, prepared from two different acetylenes and a divalent titanium alkoxide reagent, Ti(O-i-Pr)4/2 i-PrMgCl, reacted with propargyl bromide to give directly benzyltitanium compounds. The resultant benzyltitanium compounds underwent deuteriolysis, iodinolysis (with I2), or oxygenation (with O2 gas) to give the corresponding deuterium-labeled compounds, iodides, or alcohols, illustrating their synthetic versatility. The first synthesis of alcyopterosin A, a bicyclic aromatic sesquiterpenoid recently isolated and characterized, has been achieved by this method, starting with an appropriate combination of an acetylene and a diyne.

Asymmetric total synthesis of dendrobatid alkaloid 251F.

Abstract: The dendrobatid alkaloid (−)-251F was synthesized. The key steps of the synthesis were (1) an asymmetric Diels−Alder reaction to establish four of the necessary stereocenters in the target, (2) a ring-opening/ring-closing metathesis reaction to establish a key [3.3.0] bicyclic intermediate, and (3) an intramolecular Schmidt reaction.