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Query: CAS:110-02-1 (thiophene)
 5,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The explicit hydrogen version of the transferable potentials for phase equilibria (TraPPE-EH) force field is extended to benzene, pyridine, pyrimidine, pyrazine, pyridazine, thiophene, furan, pyrrole, thiazole, oxazole, isoxazole, imidazole, and pyrazole. While the Lennard-Jones parameters for carbon, hydrogen (two types), nitrogen (two types), oxygen, and sulfur are transferable for all 13 compounds, the partial charges are specific for each compound. The benzene dimer energies for sandwich, T-shape, and parallel-displaced configurations obtained for the TraPPE-EH force field compare favorably with high-level electronic structure calculations. Gibbs ensemble Monte Carlo simulations were carried out to compute the single-component vapor-liquid equilibria for benzene, pyridine, three diazenes, and eight five-membered heterocycles. The agreement with experimental data is excellent with the liquid densities and vapor pressures reproduced within 1 and 5%, respectively. The critical temperatures and normal boiling points are predicted with mean deviations of 0.8 and 1.6%, respectively.
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PMID:Transferable potentials for phase equilibria. 9. Explicit hydrogen description of benzene and five-membered and six-membered heterocyclic aromatic compounds. 1771 43

An efficient coupling route to novel pi-conjugated comonomers consisting of pyrimidine, thiophene, and bithiophene units was developed. The novel pi-donor-acceptor-donor and pi-donor-acceptor-acceptor-donor conjugated compounds were prepared by Suzuki heterocoupling and Ni(0)-mediated Ullman homocoupling reactions. Photophysical investigation of these alternating pi-donor and acceptor compounds indicated that the deactivation of their singlet excited state proceeds predominately by fluorescence and results in high fluorescence quantum yields. Intersystem crossing to the triplet state was also present in ca. 10%. Quantification of the triplet manifold by laser flash photolysis further revealed that bithiophene produced its triplet state in only 31%. Cyclic voltammetry studies showed that the comonomers undergo both oxidation and reduction leading to their radical cations and radical anions, respectively. The radical cations are highly reactive and undergo anodic polymerization resulting in mutual p- and n-type dopable polymers. The extended conjugation resulting from polymer formation was confirmed by both absorbance and fluorescence spectroscopy and by GPC. Ruthenium binding with the conjugated homocoupled ligand was also found resulting in a hybrid alternating copolymer with significantly different spectroscopic and electrochemical properties relative to its metal-free counterpart.
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PMID:Preparation, photophysics, and electrochemistry of segmented comonomers consisting of thiophene and pyrimidine units: new monomers for hybrid copolymers. 1784 27

The function of gamma-aminobutyric acid type A receptors (GABA(A) receptors) is enhanced by various clinically important drugs including benzodiazepines that act on an allosteric site formed at the interface between the alpha and gamma subunits. In contrast to classical benzodiazepines, the novel pyrazolopyrimidine indiplon (N-methyl-N-{3-[7-(thiophene-2-carbonyl)-1,5,9-triazabicyclo[4.3.0]nona-2,4,6,8-tetraen-2-yl]phenyl}acetamide; N-methyl-N-{3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidine-7-yl]phenyl}-acetamide) demonstrates relative binding selectivity for the alpha1 subunit containing receptor subtypes, which are the most frequently expressed in the mammalian central nervous system. To investigate the pharmacological properties at GABA(A) receptors and to promote the development of alpha1 subunit selective radiotracers for positron emission tomography imaging, we have started with the evaluation of various fluorinated indiplon derivatives. Binding affinities were determined in homogenates from newborn and adult rats suggesting an alpha1 preference of the reference compounds indiplon, zaleplon as well as for all newly synthesized indiplon derivatives. In homogenated cerebellar tissue obtained from adult rat brain, known to primarily express alpha1 containing GABA(A) receptors, the high affinity of the basic indiplon structure was only slightly affected by an elongation of the alkyl substituent of the amide N from methyl (indiplon; K(i) 3.1 nM) via ethyl (2a, N-(2-fluoro-ethyl)-N-{3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidine-7-yl]phenyl}-acetamide; K(i) 5.4 nM) to propyl (2b, N-(3-fluoro-propyl)-N-{3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidine-7-yl]phenyl}-acetamide; K(i) 2.4 nM). Whole cell patch-clamp recordings at neuronal and recombinant GABA(A) receptors indicated that the fluorinated derivatives 2a and 2b have a high potency at alpha1beta3gamma2L isoforms comparable to indiplon (EC(50): 105, 158, and 81 nM, respectively), with 2b displaying the most pronounced efficacy at alpha3beta3gamma2L subtypes. In conclusion, the affinity profiles and functional properties of the newly synthesised fluorinated indiplon derivatives make compounds 2a and 2b suitable for the development of [(18)F]-labelled ligands at GABA(A) receptors containing the alpha1 subunit.
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PMID:GABAA receptor pharmacology of fluorinated derivatives of the novel sedative-hypnotic pyrazolopyrimidine indiplon. 1803 50

The synthesis and photophysical evaluation of modified nucleoside analogues in which a five-membered heterocycle (furan, thiophene, oxazole and thiazole) is attached to the 5 position of 2'-deoxyuridine are reported. The furan containing derivative is identified as the most promising responsive nucleoside of this family due to its emission quantum efficiency and degree of sensitivity to its microenvironment. The furan moiety was then attached to the 5 position of 2'-deoxycytidine as well as the 8 position of adenosine and guanosine. Photophysical evaluation of these four furan containing nucleoside analogues reveal distinct differences in the absorption, emission and quantum efficiency depending upon the class of nucleoside (pyrimidine or purine). Comparing the photophysical properties of all furan containing nucleosides, identifies the furan thymidine analogue, 5-(fur-2-yl)-2'-deoxyuridine, as the best candidate for use as a responsive fluorescent probe in nucleic acids. 5-(fur-2-yl)-2'-deoxyuridine was then converted to the corresponding phosphoramidite and site specifically incorporated into DNA oligonucleotides with greater than 88% coupling efficiency. Such furan-modified oligonucleotides form stable duplexes upon hybridization to their complementary DNA strands and display favorable fluorescent features.
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PMID:Furan Decorated Nucleoside Analogues as Fluorescent Probes: synthesis, photophysical evaluation and site-specific incorporation. 1843 39

The enzymatic incorporation of a series of emissive pyrimidine analogues into RNA oligonucleotides is explored. T7 RNA polymerase is challenged with accepting three non-natural, yet related, triphosphates as substrates and incorporating them into diverse RNA transcripts. The three ribonucleoside triphosphates differ only in the modification of their uracil nucleus and include a thieno[3,2-d]pyrimidine nucleoside, a thieno[3,4-d]pyrimidine derivative, and a uridine containing a thiophene ring conjugated at its 5-position. All thiophene-containing uridine triphosphates (UTPs) get incorporated into RNA oligonucleotides at positions that are remote to the promoter, although the yields of the transcripts vary compared with the transcript obtained with only native triphosphates. Among the three derivatives, the 5-modified UTP is found to be the most "polymerase-friendly" and is well accommodated by T7 RNA polymerase. Although the fused thiophene analogues cannot be incorporated next to the promoter region, the 5-modified non-natural UTP gets incorporated near the promoter (albeit in relatively low yields) and even in multiple copies. Labeling experiments shed light on the mediocre incorporation of the fused analogues, suggesting the enzyme frequently pauses at the incorporation position. When incorporation does take place, the enzyme fails to elongate the modified oligonucleotide and yields aborted transcripts. Taken together, these results highlight the versatility and robustness, as well as the scope and limitation, of T7 RNA polymerase in accepting and incorporating reporter nucleotides into modified RNA transcripts.
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PMID:Enzymatic incorporation of emissive pyrimidine ribonucleotides. 1907 42

In situ mixtures of CdCl(2)TMEDA (0.5 equiv; TMEDA = N,N,N',N'-tetramethylethylenediamine) or InCl(3) (0.33 equiv) with [Li(tmp)] (tmp = 2,2,6,6-tetramethylpiperidino; 1.5 or 1.3 equiv, respectively) were compared with the previously described mixture of ZnCl(2)TMEDA (0.5 equiv) and [Li(tmp)] (1.5 equiv) for their ability to deprotonate anisole, benzothiazole, and pyrimidine. [(tmp)(3)CdLi] proved to be the best base when used in tetrahydrofuran at room temperature, as demonstrated by subsequent trapping with iodine. The Cd-Li base then proved suitable for the metalation of a large range of aromatics including benzenes bearing reactive functional groups (CONEt(2), CO(2)Me, CN, COPh) or heavy halogens (Br, I), and heterocycles (from the furan, thiophene, pyrrole, oxazole, thiazole, pyridine, and diazine series). Five-membered heterocycles benefiting from doubly activated positions were similarly dideprotonated at room temperature. The aromatic lithium cadmates thus obtained were involved in palladium-catalyzed cross-coupling reactions or simply quenched with acid chlorides.
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PMID:Deprotonative metalation of functionalized aromatics using mixed lithium-cadmium, lithium-indium, and lithium-zinc species. 1968 94

Some new ethyl 2-[3-(4-unsubstituted or 4-substituted phenylsufonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylates 3a-c, 2-[3-(phenylsulfonyl)ureido]-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carbohydrazides 4a-f, 3-phenylsulfonyl-6,7,8,9-tetrahydro-5H-cyclohepta[1',2':4,5]thieno[2,3-d]pyrimidine-2,4(1H,3H)dione 5 and 3-(phenylsulfonyl)-1-[3-(alkylaminocarbonyl or substituted piperazinylcarbonyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-2-yl]ureas 6a-d have been synthesized and tested for their antitumor activity. Among these compounds, 4a, 4c and 4d exhibited a broad spectrum antitumor activity with full panel (MG-MID) median growth inhibition (GI(50)) of 3.5, 4.9 and 4.0muM respectively. In addition, compounds 4c, 4d, 6c and 6d proved to be of moderate selectivity toward colon cancer cell lines with ratios of 3.1, 1.2, 3.6 and 3.0 respectively. Molecular modeling and pharmacophore prediction methods are used to study the antitumor activity of the most active compounds compared with the least active species by means of the molecular mechanic method.
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PMID:Synthesis and antitumor evaluation of novel diarylsulfonylurea derivatives: molecular modeling applications. 1993 20

2-(5-oxothiazolidinone)-cyanoacetamido derivative 3 was prepared in two steps by reaction of 2-(2-cyano-acetylamino)-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxamide (1) with phenyl isothiocyanate and chloroacetyl chloride, which diazocoupled with p-tolyldiazonium chloride in pyridine to afford the corresponding hydrazono derivative 4. Also, condensation of 3 with p-anisaldehyde gave the corresponding arylidine derivative 5. Treatment of 2 with dimethyl sulfate afforded the ketene N,S-acetal 9 which give 5-amino pyrazole derivative 10 upon treatment with hydrazine hydrate. Compound 10 was used as key intermediate for synthesis of pyrazolo[5,1-c][1,2,4]triazine 13a, b, pyrazolo[5,1-a]pyrimidine 14-17 and pyrolo pyrazole 18 derivatives. Finally, condensation of 1 with DMF-DMA afforded the corresponding acryloamide derivative 19, which afforded the corresponding pyrazole derivative 20 upon heating with hydrazine hydrate. All new synthesized compounds were evaluated as antimicrobial agents; some of them exhibited promising activities.
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PMID:Synthesis and antimicrobial activities of some new thiazole and pyrazole derivatives based on 4,5,6,7-tetrahydrobenzothiophene moiety. 2006 77

4-Amino-N-(1-phenyl-1H-pyrazol-5-yl)-benzenesulfonamide (sulfaphenazole) 1 was selected as strategic starting material for the synthesis of some novel acetamide 2, pyrrole 4, pyrrolo[2,3-d]pyrimidine 5, thiocyanate 6, hydrazone 7a,b pyrazole 8, isothiocyanate 9 and thiophene 12 derivatives to evaluate theantitumor activity. Compound 4 was more effective than the reference drug, doxorubicin (CAS 23214-92-8) as positive control.
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PMID:Novel antitumor acetamide, pyrrole, pyrrolopyrimidine, thiocyanate, hydrazone, pyrazole, isothiocyanate and thiophene derivatives containing a biologically active pyrazole moiety. 2010 54

Novel derivatives of cyclopentathienopyrimidinediones 6, pyridothienopyrimidinediones 7, ethyl cycloheptathiophene-3-carboxylates 10, ethyl tetrahydrothienopyridine-3-carboxylates 11, tetrahydrocycloheptathienopyrimidin-4(3H)-ones 12, tetrahydrotriazolobenzothienopyrimidin-5(4H)-ones 17 and tetrahydro-5H-cycloheptathienopyrimidin-4(3H)-ones 21 have been synthesized and tested for their 5-HT2A antagonist activity. Preliminary pharmacological studies showed that compounds 3-[2-[4-phenylpiperazin-1-yl]ethyl]-6,7-dihydro-5H-cyclopenta[b]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione 6a and ethyl 2-[[4-(2-methoxyphenyl)piperazin-1-yl]acetylamino]-4,5,6,7-tetrahydro-6-methylthieno[2,3-c]pyridine-3-carboxylate 11d were found to be the most active molecules as 5-HT2A antagonists. Molecular modeling and pharmacophore prediction methodology are used to study the structural features required for 5-HT2A antagonist properties of the active compounds compared with nonactive species by means of the molecular mechanic method. The 2-methoxy substituent in the structure of 11d seems to be necessary for its full antagonistic properties. Optimal placement of basic nitrogen relative to the plane of thiophene core was found to have a profound effect on affinity and biological activity.
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PMID:Synthesis and pharmacological evaluation of novel fused thiophene derivatives as 5-HT2A receptor antagonists: molecular modeling study. 2014 93


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