- FT-IR Spectrometric Study of N-t-Butoxycarbonylglycine N',N'-dimethylamide and its Interaction with Proton Donors
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FT-IR spectra of N-t-butoxycarbonylglycine-N',N'-dimethylamide and its deuteriated ND counterpart, in solution and in the solid state, have been analysed between 3800 and 400 cm-1.An assignment is proposed for some important vibrations, especially for the so-called amide vibrations, by comparison with literature data on similar molecules.The frequency shifts and intensity changes of the vibrations sensitive to the physical state of this model dipeptide strongly suggest that intermolecular hydrogen bonds involving mainly the NH and C=O (amide) groups are formed in the solid state.Thermodynamic parameters (equilibrium constants and enthalpies) of the hydrogen-bond formation with phenol derivatives have been determined in carbon tetrachloride and in 1,2-dichloroethane.The complexes investigated are of medium strength.The FT-IR spectra in the νC=O region and the double perturbation of the νNH band assigned to the five-membered intramolecular NH...O=C hydrogen-bonded ring clearly show that complex formation occurs at both the amide and urethane carbonyl groups.About 45percent of the complexes are formed on the C=O (urethane) function, almost independent of the acidity of the phenols.The unusual broadness of the OH...O=C complex band originates from the superposition of two complex bands.N-t-Butoxycarbonylglycine-N',N'-dimethylamide can be considered as being built up from two model molecules, methyl-N-methylcarbamate and N,N-dimethylacetamide.
- Parmentier, J.,Samyn, C.,Beylen, M. Van,Zeegers-Huyskens, Th.
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- IMPROVED INHIBITORS OF THE NOTCH TRANSCRIPTIONAL ACTIVATION COMPLEX AND METHODS FOR USE OF THE SAME
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Disclosed herein are inhibitors of the Notch transcriptional activation complex, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein can include compounds of Formula (I) and pharmaceutically accept
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Paragraph 0090
(2020/10/21)
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- Highly Selective and Sensitive Detection of Biogenic Defense Phytohormone Salicylic Acid in Living Cells and Plants Using a Novel and Viable Rhodamine-Functionalized Fluorescent Probe
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Detecting plant-derived signal molecules using fluorescent probes is a key topic and a huge challenge for scientists. Salicylic acid (SA), a vital plant-derived defense hormone, can activate global transcriptional reprogramming to systemically express a network of prominent pathogenesis-related proteins against invasive microorganisms. This strategy is called systemic acquired resistance (SAR). Therefore, monitoring the dynamic fluctuations of SA in subcellular microenvironments can advance our understanding of different physiological and pathological functions during the SA-induced SAR mechanism, thus benefiting the discovery and development of novel immune activators that contribute to crop protection. Here, detection of signaling molecule SA in plant callus tissues was first reported and conducted by a simple non-fluorescent rhodamine-tagged architecture bearing a flexible 2-amino-N,N-dimethylacetamide pattern. This study can markedly advance and promote the usage of fluorescent SA probes for distinguishing SA in the plant kingdom.
- Fu, Yi-Hong,Li, Wen,Li, Zhong,Ouyang, Gui-Ping,Wang, Pei-Yi,Wang, Zhen-Chao,Wen, Xiao-Peng,Yang, Lin-Lin,Yang, Song,Zou, Si-Yan
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p. 4285 - 4291
(2020/05/14)
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- LIT-001, the First Nonpeptide Oxytocin Receptor Agonist that Improves Social Interaction in a Mouse Model of Autism
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Oxytocin (OT) and its receptor (OT-R) are implicated in the etiology of autism spectrum disorders (ASD), and OT-R is a potential target for therapeutic intervention. Very few nonpeptide oxytocin agonists have currently been reported. Their molecular and in vivo pharmacology remain to be clarified, and none of them has been shown to be efficient in improving social interaction in animal models relevant to ASD. In an attempt to rationalize the design of centrally active nonpeptide full agonists, we studied in a systematic way the structural determinants of the affinity and efficacy of representative ligands of the V1a and V2 vasopressin receptor subtypes (V1a-R and V2-R) and of the oxytocin receptor. Our results confirm the subtlety of the structure-affinity and structure-efficacy relationships around vasopressin/oxytocin receptor ligands and lead however to the first nonpeptide OT receptor agonist active in a mouse model of ASD after peripheral ip administration.
- Frantz, Marie-Céline,Pellissier, Lucie P.,Pflimlin, Elsa,Loison, Stéphanie,Gandiá, Jorge,Marsol, Claire,Durroux, Thierry,Mouillac, Bernard,Becker, Jér?me A. J.,Le Merrer, Julie,Valencia, Christel,Villa, Pascal,Bonnet, Dominique,Hibert, Marcel
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p. 8670 - 8692
(2018/10/05)
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- Structural studies of β-turn-containing peptide catalysts for atroposelective quinazolinone bromination
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We describe herein a crystallographic and NMR study of the secondary structural attributes of a β-turn-containing tetra-peptide, Boc-Dmaa-d-Pro-Acpc-Leu-NMe2, which was recently reported as a highly effective catalyst in the atroposelective bromination of 3-arylquinazolin-4(3H)-ones. Inquiries pertaining to the functional consequences of residue substitutions led to the discovery of a more selective catalyst, Boc-Dmaa-d-Pro-Acpc-Leu-OMe, the structure of which was also explored. This new lead catalyst was found to exhibit a type I′ β-turn secondary structure both in the solid state and in solution, a structure that was shown to be an accessible conformation of the previously reported catalyst, as well.
- Metrano,Abascal,Mercado,Paulson,Miller
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supporting information
p. 4816 - 4819
(2016/04/09)
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- Design and synthesis of novel diamide derivatives of glycine as antihyperglycemic agents
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DPP-4 inhibition is one of the most extensively explored approaches for the management of type 2 diabetes (T2D). Most DPP-4 inhibitors in the market contain a proline mimetic active pharmacophore. Herein, we report the design, synthesis, and preliminary e
- Sharma, Radhika,Soman, Shubhangi S.
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supporting information
p. 1307 - 1317
(2016/08/16)
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- Enantioselective Synthesis of 3-Arylquinazolin-4(3H)-ones via Peptide-Catalyzed Atroposelective Bromination
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We report the development of a tertiary amine-containing β-turn peptide that catalyzes the atroposelective bromination of pharmaceutically relevant 3-arylquinazolin-4(3H)-ones (quinazolinones) with high levels of enantioinduction over a broad substrate scope. The structure of the free catalyst and the peptide-substrate complex were explored using X-ray crystallography and 2D-NOESY experiments. Quinazolinone rotational barriers about the chiral anilide axis were also studied using density functional theory calculations and are discussed in light of the high enantioselectivities observed. Mechanistic studies also suggest that the initial bromination event is stereodetermining, and the major monobromide intermediate is an atropisomerically stable, mono-ortho-substituted isomer. The observation of stereoisomerically stable monobromides stimulated the conversion of the tribromide products to other atropisomerically defined products of interest. For example, (1) a dehalogenation Suzuki-Miyaura cross-coupling sequence delivers ortho-arylated derivatives, and (2) a regioselective Buchwald-Hartwig amination procedure installs para-amine functionality. Stereochemical information was retained during these subsequent transformations.
- Diener, Matthew E.,Metrano, Anthony J.,Kusano, Shuhei,Miller, Scott J.
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supporting information
p. 12369 - 12377
(2015/10/12)
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- Peptide-catalyzed conversion of racemic oxazol-5(4 H)-ones into enantiomerically enriched α-amino acid derivatives
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We report the development and optimization of a tetrapeptide that catalyzes the methanolytic dynamic kinetic resolution of oxazol-5(4H)-ones (azlactones) with high levels of enantioinduction. Oxazolones possessing benzylic-type substituents were found to perform better than others, providing methyl ester products in 88:12 to 98:2 er. The mechanism of this peptide-catalyzed process was investigated through truncation studies and competition experiments. High-field NOESY analysis was performed to elucidate the solution-phase structure of the peptide, and we present a plausible model for catalysis.
- Metrano, Anthony J.,Miller, Scott J.
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p. 1542 - 1554
(2014/03/21)
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- Copper-catalyzed oxidative coupling of carboxylic acids with N,N-dialkylformamides: An approach to the synthesis of amides
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A new synthetic approach for amide bond formation through the oxidative coupling of N,N-dialkylformamides with carboxylic acids was achieved by using a copper catalyst. Furthermore, this method was applied in the coupling of chiral amino acids in which the stereochemistry was retained in the resulting amide products. A new synthetic approach to amide bond formation through the oxidative coupling of N,N-dialkylformamides with carboxylic acids was achieved by using a copper catalyst and aqueous tert-butyl hydroperoxide (TBHP) as a sacrificial oxidant. Furthermore, this method was applied in the coupling of chiral amino acids in which the stereochemistry was retained in the resulting amide products. Copyright
- Kumar, P. Santhosh,Kumar, G. Sathish,Kumar, R. Arun,Reddy, N. Veera,Rajender Reddy
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supporting information
p. 1218 - 1222
(2013/04/10)
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- Direct catalytic formation of primary and tertiary amides from non-activated carboxylic acids, employing carbamates as amine source
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The operationally simple titanium(IV)- or zirconium(IV)-catalyzed direct amidation of non-activated carboxylic acids with ammonium carbamates generates primary, and tertiary N,N-dimethyl-substituted amides in good to excellent yields. Copyright
- Tinnis, Fredrik,Lundberg, Helena,Adolfsson, Hans
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supporting information
p. 2531 - 2536
(2012/11/06)
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- NOVEL 3,5-DISUBSTITUED-3H-IMIDAZO[4,5-B]PYRIDINE AND 3,5- DISUBSTITUED -3H-[1,2,3]TRIAZOLO[4,5-B] PYRIDINE COMPOUNDS AS MODULATORS OF PROTEIN KINASES
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The present invention provides, inter alia, compounds of formula ΙΑ,ΙΙΑ and III as protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of kinase mediated diseases or disorders with them.
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Page/Page column 117
(2011/12/04)
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- 1,3-Dihydro-2H-Indole-2-One Compound and Pyrrolidine-2-One Compound Fused With Aromatic Heterocycle
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It is intended to provide a drug which is efficacious against pathological conditions relating to arginine-vasopressin V1b receptor. More particularly speaking, it is intended to provide a drug which has a therapeutic or preventive effect on depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug addiction, epilepsy, brain infarction, brain ischemia, brain edema, head injury, inflammation, immune diseases, alopecia and so on. As the results of intensive studies, a novel 1,3-dihydro-2H-indol-2-one compound and a pyrrolidin-2-one compound fused with a heteroaromatic ring, which are highly selective antagonists of arginine-vasopressin V1b receptor, have high metabolic stabilities and show favorable brain penetration and high plasma concentrations, are found, thereby achieving the above objective.
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Page/Page column 80
(2009/01/24)
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- Deuterium exchange as an indicator of hydrogen bond donors and acceptors
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Hydrogen-deuterium exchange has been used to determine the hydrogen bonding preferences of a select group of small peptides in organic solvents. This kinetic analysis permitted comparison of hydrogen bond strengths in relation to controls and also indicated the identity of both hydrogen bond donors and hydrogen bond acceptors. Copyright
- Steffel, Lauren R.,Cashman, Timothy J.,Reutershan, Michael H.,Linton, Brian R.
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p. 12956 - 12957
(2008/09/17)
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- Conformational analysis of β-turn structure in tetrapeptides containing proline or proline analogs
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In order to evaluate the influence of cyclic secondary amino acids on the stability of β-turn structure, we have prepared Ac-Gly-L-Xxx-L-Leu-Gly-N(CH3)2 (Xxx = Aze, 4-membered ring: 1, Xxx = Pro, 5-membered ring: 2, Xxx = Pip, 6-membered ring: 3). The NOE cross peaks that support β-turn structure were observed in 1-3. The NOE cross peak between both terminals of the synthetic peptides, however, was observed only in the NOESY spectra of 2. This result indicates that 5-membered ring side chain in proline plays a very important role in the formation of β-hairpin structure.
- Hayashi, Takashi,Asai, Tomohito,Ogoshi, Hisanobu
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p. 3039 - 3042
(2007/10/03)
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