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Indole Ring (indole + ring)
Selected AbstractsSynthesis of 5-Methylindole-4,7-quinone Through a New Construction of the Functionalized Indole Ring Based on the Allene-Mediated Electrocyclic Reaction Involving the Pyrrole[b]-Bond.CHEMINFORM, Issue 50 2004Maho Hirayama Abstract For Abstract see ChemInform Abstract in Full Text. [source] Electrophilic S -Trifluoromethylation of Cysteine Side Chains in , - and , -Peptides: Isolation of Trifluoro-methylated Sandostatin® (Octreotide) DerivativesHELVETICA CHIMICA ACTA, Issue 11 2008Stefania Capone Abstract The new electrophilic trifluoromethylating 1-(trifluoromethyl)-benziodoxole reagents A and B (Scheme,1) have been used to selectively attach CF3 groups to the S-atom of cysteine side chains of , - and , -peptides (up to 13-residues-long; products 7,14). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2-position). The products are purified by chromatography, and identified by 1H-, 13C-, and 19F-NMR spectroscopy, by CD spectroscopy, and by high-resolution mass spectrometry. The CF3 groups, thus introduced, may be replaced by H (Na/NH3), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin-labelling, imaging, PET) are discussed. [source] Transition Metal-Catalysed, Direct and Site-Selective N1-, C2- or C3-Arylation of the Indole Nucleus: 20 Years of ImprovementsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 5 2009Lionel Joucla Abstract The direct and site-selective transition metal-catalysed N1-, C2- or C3-arylations of indoles have been the subject of almost continuous improvements since their discovery in early 1980s. This research area is mainly motivated by the biological relevance of this class of compounds in order to propose catalytic alternative syntheses to the well known methodologies involving the formation of the indole ring like the Fischer, Larock, Cacchi, Lautens etc. reactions. Since the late 1990s it has experienced new impulses related to the intensive development of catalytic CH activation. Today, through the intensive studies of Buchwald and Hartwig, the N1-arylation of indoles has reached sufficient maturity for both academic and industrial applications. On the other hand, the selective C2- or C3-arylation of indoles, initiated by Ohta in the middle 1980s, has become a hot research area these last years following the reports of Sames. Surprisingly, only few reports concern the use of heterogeneous catalysts; however, the application of these emerging methodologies seems to be related to the discovery of industrially attractive systems. [source] Indole ring orientations of Trp189 in the ground and M intermediate states of bacteriorhodopsin as studied by polarized UV resonance Raman spectroscopy,JOURNAL OF RAMAN SPECTROSCOPY, Issue 1-3 2006Kazuhiro Asakawa Abstract Polarized resonance Raman spectroscopy provides a means for orientation analysis of proteins in aligned samples. Previously, we developed a Raman linear intensity difference (RLID) method to determine the orientations of aromatic amino acid side chains in flow-oriented or membrane-bound proteins. In this study, we have applied the RLID method to Trp189 in bacteriorhodopsin (BR), a transmembrane protein that acts as a light-driven proton pump. Among the eight Trp residues in BR, the Raman spectrum of Trp189 has been extracted by subtracting the spectrum of the Trp189 , Phe mutant from that of wild-type BR. By examining the 251.3-nm-exited polarized resonance Raman intensities of two indole ring vibrations of Trp189, the directions of the La and Bb transition moments have been determined with respect the membrane normal in the light-adapted ground state (BR568) and a photo-excited intermediate (M). Comparison of the orientations of the Trp189 indole ring derived from the La and Bb inclination angles has shown that the indole ring slightly but significantly reorients toward the ionone ring of the retinal chromophore in the M intermediate. The reorientation of Trp189 is consistent with the previous observation that helix F, on which Trp189 is located, undergoes an outward tilt and the hydrophobic interaction of Trp189 increases in the M intermediate. The RLID method combined with 251.3 nm excitation and point mutation is useful for detecting even a small reorientation of a targeted Trp residue. Copyright © 2006 John Wiley & Sons, Ltd. [source] Toward the development of new medicinal leads with selectivity for protein kinase C isozymesTHE CHEMICAL RECORD, Issue 4 2005Kazuhiro Irie Abstract Tumor promoters such as phorbol esters bind strongly to protein kinase C (PKC) isozymes to induce their activation. Since each PKC isozyme is involved in diverse biological events in addition to tumor promotion, the isozymes serve as promising therapeutic targets. Tumor promoters bind to the C1A and/or C1B domain of conventional (,, ,I, ,II, and ,) and novel PKC isozymes (,, ,, ,, and ,). As these C1 domains play differential roles in PKC activation and their translocation in cells, the development of agents with binding selectivity for individual C1 domains is a pressing need. For this purpose, we established a synthetic C1 peptide library of all PKC isozymes. The library enabled us to identify indolactam-V (1) as a promising lead compound. Our diverse structure,activity studies on 1 indicated that the position of the hydrophobic substituent on the indole ring dominates the PKC isozyme- and C1 domain-selective binding rather than conformation of the nine-membered lactam. Moreover, we suggested that the indole ring of 1 could be involved in the CH/, interaction with Pro-11 of the C1B domain of PKC,. This invaluable information will lead to the structural optimization of the PKC, ligand as exemplified by the design and synthesis of naphtholactam-V8 (21). © 2005 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 5: 185,195; 2005: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20044 [source] Halide salts of antimigraine agents eletriptan and naratriptanACTA CRYSTALLOGRAPHICA SECTION C, Issue 12 2008K. Ravikumar Molecules of eletriptan hydrobromide monohydrate (systematic name: (1S,2R)-1-methyl-2-{5-[2-(phenylsulfonyl)ethyl]-1H -indol-3-ylmethyl}pyrrolidinium bromide monohydrate), C22H27N2O2S+·Br,·H2O, (I), and naratriptan hydrochloride (systematic name: 1-methyl-4-{5-[2-(methylsulfamoyl)ethyl]-1H -indol-3-yl}piperidinium chloride), C17H26N3O2S+·Cl,, (II), adopt conformations similar to other triptans. The C-2 and C-5 substituents of the indole ring, both of which are in a region of conformational flexibility, are found to be oriented on either side of the indole ring plane in (I), whilst they are on the same side in (II). The N atom in the C-2 side chain is protonated in both structures and is involved in the hydrogen-bonding networks. In (I), the water molecules create helical hydrogen-bonded chains along the c axis. In (II), the hydrogen bonding of the chloride ions results in macrocyclic R42(20) and R42(24) ring motifs that form sheets in the bc plane. This structural analysis provides an insight into the molecular structure,activity relationships within this class of compound, which is of use for drug development. [source] Novel Fused Pyrrole Heterocyclic Ring Systems as Structure Analogs of LE 300: Synthesis and Pharmacological Evaluation as Serotonin 5-HT2A, Dopamine and Histamine H1 Receptor LigandsARCHIV DER PHARMAZIE, Issue 2 2010Sherif A. F. Rostom Abstract LE 300 represents a structurally novel type of antagonists acting preferentially at the dopamine D1/D5 receptors and the serotonin 5-HT2A receptor. This compound consists of a ten-membered central azecine ring fused to an indole ring on one side and a benzene moiety on the other side. To estimate the importance of the indole and / or phenyl moieties in this highly active benz-indolo-azecine, both rings were removed and replaced with a 1H -pyrrole counterpart. Accordingly, some new analogs of LE 300 namely, pyrrolo[2,3- g]indolizine, pyrrolo[3,2- a]quinolizine rings and their corresponding dimethylpyrrolo[2,3- d]azonine, and dimethylpyrrolo[2,3- d]azecine were synthesized to be evaluated for their activity at the 5-HT2A and dopamine D1, D2L, D4, D5 receptors in relation to LE 300. In addition, their activity at the H1 -histamine receptors was also determined. The results suggested that the rigid pyrrolo[2,3- g]indolizine 7 and pyrrolo[3,2- a]quinolizine 8 analogs lacked biological activity in the adopted three bioassays. However, their corresponding flexible pyrrolo[2,3- d]azonine 11 and pyrrolo[2,3- d]azecine 12 derivatives revealed weak partial agonistic activity and weak antagonistic potency at the serotonin 5-HT2A and histamine H1 receptors, respectively. Meanwhile, they showed no affinity to any of the four utilized dopamine receptors. Variation in ring size did not contribute to a significant influence on the three tested bioactivities. Removal of the hydrophobic moiety (phenyl ring) and replacement of the indole moiety with a 1H -pyrrole counterpart led to a dramatic alteration in the profile of activity of such azecine-type compounds. [source] Surface-enhanced Raman difference between bombesin and its modified analogues on the colloidal and electrochemically roughen silver surfacesBIOPOLYMERS, Issue 10 2008Edyta Podstawka Abstract In this article, surface-enhanced Raman scattering (SERS) spectra of bombesin (BN) and its six modified analogues ([D-Phe12]BN, [Tyr4]BN, [Tyr4,D-Phe12]BN, [D-Phe12,Leu14]BN, [Leu13 -®-Leu14]BN, and [Lys3]BN) on a colloidal silver surface are reported and compared with SERS spectra of these species immobilized onto an ellectrochemically roughen silver electrode. Changes in enhancement and wavenumber of proper bands upon adsorption on different silver surfaces are consistent with BN and its analogues adsorption primarily through Trp8. Slightly different adsorption states of these molecules are observed depending upon natural amino acids substitution. For example, the indole ring in all the peptides interacts with silver nanoparticles in a edge-on orientation. It is additionally coordinated to the silver through the N1H bond for all the peptides, except [Phe12]BN. This is in contrary to the results obtained for the silver roughen electrode that show direct but not strong N1H/Ag interaction for all peptides except [D-Phe12,Leu14]BN and [Leu13 -®-Leu14]BN. For BN only CO is not involved in the chemical coordination with the colloidal surface. [Lys3]BN and BN also adsorb with the CN bond of NH2 group normal and horizontal, respectively, to the colloidal surface, whereas CNH2 in other peptides is tilted to this surface. Also, the Trp8 CH2 moiety of only [Tyr4]BN, [Lys3]BN, and [Tyr4,D-Phe12]BN coordinates to Ag, whereas the Phe12 ring of [Phe12]BN, [Tyr4,D-Phe12]BN, and [D-Phe12,Leu14]BN assists in the peptides binding only on the colloidal silver. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 807,819, 2008. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Investigation of molecular structure of bombesin and its modified analogues nonadsorbed and adsorbed on electrochemically roughened silver surfaceBIOPOLYMERS, Issue 6 2008Edyta Podstawka Abstract This work describes the molecular structure of bombesin (BN) and its analogs on the basis of the absorption infrared and Raman results described below. In these analogues is replaced one ([D-Phe12]BN, [Tyr4]BN, and [Lys3]BN) or two ([Tyr4,D-Phe12]BN, [D-Phe12,Leu14]BN, and [Leu13 -®-Leu14]BN) amino acid residues within the peptide chain with a synthetic amino acid, creating antagonists to bombesin, which are useful in the treatment of cancer. It is also used surface enhanced Raman scattering (SERS) to study the differences and changes in the vibrational spectra of BN and its analogs, which were attached to an electrochemically roughened silver surface as these peptides interacted with target proteins. This work explores the use of SERS for molecules anchored to a macroscopic silver surface to interrogate the interaction of these peptides with protein receptors. The results presented here show that all peptides coordinate to the macroscopic silver surface through an indole ring and the methylene group of Trp8, the CO fragment, and an amide bond; however, the orientation of these fragments on the electrochemically roughened silver surface and the strength of the interactions with this surface is slightly different for each peptide. For example, the interaction of CH2 of [D-Phe12]BN, [Tyr4,D-Phe12]BN, [D-Phe12,Leu14]BN, [Leu13 -®-Leu14]BN, and [Lys3]BN with the silver surface perturbed the vertical orientation of the Trp8 indole ring on this surface. Hence, the indole ring adopted a close to perpendicular orientation on the silver surface for BN and [Tyr4]BN, only. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 506,521, 2008. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Reinvestigation of a Cyclic Dipeptide N -Prenyltransferase Reveals Rearrangement of N-1 Prenylated Indole DerivativesCHEMBIOCHEM, Issue 7 2008Han-Li Ruan Prof. Dr. Converting revere to regular: Reinvestigation of cyclic dipeptide N -prenyltransferase (CdpNPT) revealed that the enzymatic products are derivatives that carry 3,-(3,,3,)-dimethylallyl moieties at the N-1 position of the indole ring, and they undergo rearrangement in the presence of acids, such as trichloroacetic acid, used for termination of enzymatic reactions and protein precipitation (see scheme). The rearrangement can be avoided by using MeOH instead of acid for termination and protein precipitation. [source] The effect of temperature and lipid on the conformational transition of gramicidin A in lipid vesicles,BIOPOLYMERS, Issue 4 2005Ta-Hsien Lin Abstract The present study investigated the effect of temperature and lipid/peptide molar ratio on the conformational changes of the membrane peptide gramicidin A from a double-stranded helix to a single-stranded helical dimmer in 1,2-dimyristoyl-glycerol-3-phosphochloine (DMPC) vesicles. Tryptophan fluorescence spectroscopy results suggested that the conformational transition fitted a three-state (two-step) "folding" model. Rate constants, k1 and k2, were determined for each of the two steps. Since k1 and k2 increased with an increase in temperature, we hypothesized that the process corresponded to the breakage and formation of the backbone hydrogen bonds. The k1 was from 10 to 45 folds faster than k2, except for lipid/peptide molar ratios above 89.21, where k2 increased rapidly. At molar ratios below 89.21, k2 was insensitive to changes in lipid concentration. To account for this phenomenon, we proposed that while the driving interaction at high molar ratios is between the indole rings of the tryptophan residues and the lipid head groups, at low molar ratios there may be an intermolecular interaction between the tryptophan residues that causes gramicidin A to form an organized aggregated network. This aggregated network, caused by the tryptophan,tryptophan interaction, may be the main effect responsible for the slow down of the conformation change. © 2005 Wiley Periodicals, Inc. Biopolymers 78: 179,186, 2005 [source] | |||||||||||||||||||