- Synthesis and Stereochemical Assignment of Conioidine A: DNA- And HSA-Binding Studies of the Four Diastereomers
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Conioidine A (1), isolated in 1993 with unknown relative and absolute configuration, was suggested to be a DNA-binding compound by an indirect technique. Four stereoisomers of conioidine A have been synthesized from d- and l-proline, and the natural product has been identified as possessing (4R,6R) absolute configuration. Binding of the conioidine diastereomers to calf thymus DNA (CT DNA) and human serum albumin (HSA) has been investigated by fluorescence spectroscopy and isothermal titration calorimetry (ITC). All stereoisomers display at least an order of magnitude weaker binding to DNA than the control compound netropsin; however, a strong association with HSA was observed for the (4R,6S) stereoisomer.
- Shaktah, Ryan,Vardanyan, Laura,David, Elroma,Aleman, Alexis,Orr, Dupre,Shaktah, Lawrence A.,Tamae, Daniel,Minehan, Thomas
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supporting information
p. 3191 - 3198
(2020/11/03)
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- Pyrrolidine-Oxadiazolone Conjugates as Organocatalysts in Asymmetric Michael Reaction
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Pyrrolidine-oxadiazolone based organocatalysts are envisaged, synthesized, and utilized for asymmetric Michael reactions. Results of the investigations suggest that some of the catalysts are indeed efficient for stereoselective 1,4-conjugated Michael additions (dr: >97:3, ee up to 99%) in high chemical yields (up to 97%) often in short reaction time. As an extension, one enantiopure Michael adduct has been utilized to synthesize optically active octahydroindole.
- Mahato, Chandan K.,Mukherjee, Sayan,Kundu, Mrinalkanti,Pramanik, Animesh
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p. 1053 - 1063
(2019/01/14)
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- METHODS OF TREATING LIVER DISEASES
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The invention provides tricyclic compounds and their use in treating liver disorders, such as non-alcoholic steatohepatitis and related disorders (e.g., fibrosis). The compounds are contemplated to have activity against methionyl aminopeptidase 2.
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Paragraph 00410; 00415
(2014/05/24)
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- PARTIALLY SATURATED TRICYCLIC COMPOUNDS AND METHODS OF MAKING AND USING SAME
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The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
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Page/Page column 181; 182
(2012/12/13)
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- Synthesis and biological evaluation of potential 5-HT7 receptor PET radiotracers
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Brain serotonin 7 receptor (5-HT7) is involved in several mood disorders and drug candidates targeting this subtype are currently in development. Positron emission tomography (PET) is a molecular imaging modality offering great promise for accelerating the process from preclinical discovery to clinical phases. As no PET radiopharmaceutical has yet been used successfully to study the 5-HT7 receptor in vivo, our objective is to develop the first 5-HT7 fluorine-18 labeled radiotracer. Four structural analogs of SB269970, a specific 5-HT7 receptor antagonist, divided in FP3 series and FPMP series were synthesized. Their antagonist effects were investigated by cellular functional assay. Nitro-precursors of these analogs were radiolabeled via a [18F-]nucleophilic substitution and in vitro autoradiographies were performed in rat brain. Chemical and radiochemical purities of fluorine radiotracers were >99% with specific activities in 40-129 GBq/μmole range. The four derivates presented antagonism potencies toward 5-HT7 receptors (pKB) between 7.8 and 8.8. The four PET radiotracers had suitable characteristic for 5-HT7 receptor probing in vitro even if the FP3 series seemed to be more specific for this receptor. These results encourage us to pursue in vivo studies.
- Andries, Julien,Lemoine, Laetitia,Le Bars, Didier,Zimmer, Luc,Billard, Thierry
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p. 3455 - 3461
(2011/08/03)
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- SUBSTITUTED BENZHYDRYLETHERS
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Disclosed herein are substituted benzhydrylethers of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of their use thereof.
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Page/Page column 33
(2009/08/18)
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- Transition state analogue discrimination by related purine nucleoside phosphorylases
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Transition state analogues of PNP, the Immucillins and DADMe-Immucillins, were designed to match transition state features of bovine and human PNPs, respectively. The inhibitors with or without the hydroxyl and hydroxymethyl groups of the substrate demonstrate that inhibitor geometry mimicking that of the transition state confers binding affinity discrimination. This finding is remarkable since crystallographic analysis indicates complete conservation of active site residues and contacts to ligands in human and bovine PNPs. Copyright
- Taylor Ringia, Erika A.,Tyler, Peter C.,Evans, Gary B.,Furneaux, Richard H.,Murkin, Andrew S.,Schramm, Vern L.
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p. 7126 - 7127
(2007/10/03)
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- INHIBITORS OF HUMAN TUMOR-EXPRESSED CCXCKR2
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Pharmaceutical compositions containing organic compounds or salts thereof that serve as modulators for the SDF-1 or I-TAC chemokines are disclosed. The compounds and compositions are useful in the treatment of cancer, especially in the inhibition of cancer proliferation, growth, and metastasis. Methods of interfering with SDF-1 and/or I-TAC binding to the CCXCKR2 receptor and treating cancer using the compounds and pharmaceutical compositions of the present invention are also disclosed.
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- Endomorphin-1 analogues containing β-proline are μ-opioid receptor agonists and display enhanced enzymatic hydrolysis resistance
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In this paper we describe the synthesis and affinity toward the μ-opioid receptor of some tetrapeptides obtained from endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2 (1), by substituting each amino acid in turn with its homologue. The ability to bind μ -opioid receptors depends on the β-amino acid, and in particular 4, which contains β-L-Pro, has a KI, in the nanomolar range. The peptides 4 and 5 are significantly more resistant to enzymatic hydrolysis than 1. The same compounds, as well as the μ-opioid receptor agonist DAMGO, produced a concentration-dependent inhibition of forskolin-stimulated cyclic AMP formation, thus behaving as μ-opioid agonists. These features suggest that this novel class of endomorphin-1 analogues may represent suitable candidates for the in vivo investigation as potential μ-opioid receptor agonists.
- Cardillo, Giuliana,Gentilucci, Luca,Qasem, Ahmed R.,Sgarzi, Fabio,Spampinato, Santi
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p. 2571 - 2578
(2007/10/03)
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