99124-56-8Relevant articles and documents
Annelated Pyridine Bases for the Selective Acylation of 1,2-Diols
Mayr, Stefanie,Zipse, Hendrik
supporting information, (2022/03/08)
A set of 24 annelated derivatives of 4-diaminopyridine (DMAP) has been synthesized and tested with respect to its catalytic potential in the regioselective acylation of 1,2-diol substrates. The Lewis basicities of the catalysts as quantified through quantum chemical calculations vary due to inductive substituent effects and intramolecular stacking interactions between side chain π-systems and the pyridinium core ring system. The primary over secondary hydroxyl group selectivities in catalytic acylations of 1,2-diol substrates depend on the size and the steric demand of the Lewis base and the anhydride reagent.
Synthesis and structural characterization of a monocarboxylic inhibitor for GRB2 SH2 domain
Xiao, Tao,Sun, Luxin,Zhang, Min,Li, Zilu,Haura, Eric B.,Schonbrunn, Ernst,Ji, Haitao
supporting information, (2021/09/14)
A monocarboxylic inhibitor was designed and synthesized to disrupt the protein–protein interaction (PPI) between GRB2 and phosphotyrosine-containing proteins. Biochemical characterizations show compound 7 binds with the Src homology 2 (SH2) domain of GRB2 and is more potent than EGFR1068 phosphopeptide 14-mer. X-ray crystallographic studies demonstrate compound 7 occupies the GRB2 binding site for phosphotyrosine-containing sequences and reveal key structural features for GRB2–inhibitor binding. This compound with a –1 formal charge offers a new direction for structural optimization to generate cell-permeable inhibitors for this key protein target of the aberrant Ras-MAPK signaling cascade.
Cyclohexyl-Fused, Spirobiindane-Derived, Phosphine-Catalyzed Synthesis of Tricyclic ?3-Lactams and Kinetic Resolution of ?3-Substituted Allenoates
Wu, Mingyue,Han, Zhaobin,Li, Kaizhi,Wu, Ji'En,Ding, Kuiling,Lu, Yixin
, p. 16362 - 16373 (2019/10/16)
A C2-symmetric chiral phosphine catalyst, NUSIOC-Phos, which can be easily derived from cyclohexyl-fused spirobiindane, was introduced. A highly enantioselective domino process involving pyrrolidine-2,3-diones and γ-substituted allenoates catalyzed by NUSIOC-Phos has been disclosed. Diastereospecific tricyclic γ-lactams containing five contiguous stereogenic centers were obtained in high yields and with nearly perfect enantioselectivities. A kinetic resolution process of racemic γ-substituted allenoates was developed for the generation of optically enriched chiral allenoates.
Selective Inhibitors of a Human Prolyl Hydroxylase (OGFOD1) Involved in Ribosomal Decoding
Thinnes, Cyrille C.,Lohans, Christopher T.,Abboud, Martine I.,Yeh, Tzu-Lan,Tumber, Anthony,Nowak, Rados?aw P.,Attwood, Martin,Cockman, Matthew E.,Oppermann, Udo,Loenarz, Christoph,Schofield, Christopher J.
supporting information, p. 2019 - 2024 (2019/01/11)
Human prolyl hydroxylases are involved in the modification of transcription factors, procollagen, and ribosomal proteins, and are current medicinal chemistry targets. To date, there are few reports on inhibitors selective for the different types of prolyl hydroxylases. We report a structurally informed template-based strategy for the development of inhibitors selective for the human ribosomal prolyl hydroxylase OGFOD1. These inhibitors did not target the other human oxygenases tested, including the structurally similar hypoxia-inducible transcription factor prolyl hydroxylase, PHD2.
Synthesis and DNA-cleaving activity of lactenediynes conjugated with DNA-complexing moieties
Banfi, Luca,Basso, Andrea,Bevilacqua, Elisabetta,Gandolfo, Valentina,Giannini, Giuseppe,Guanti, Giuseppe,Musso, Loana,Paravidino, Monica,Riva, Renata
, p. 3501 - 3518 (2008/09/21)
Lactenediynes are compounds characterized by the fusion of a β-lactam with a cyclodeca-3-ene-1,5-diyne. In this work the most promising members of this family have been activated by attaching a carbalkoxy or a carbamoyl group to the azetidinone nitrogen, and conjugated to various DNA-complexing moieties, either acting by intercalation or through groove binding. These conjugated artificial enediynes have been demonstrated to possess in vitro ability to produce single and double strand cleavage of plasmid DNA. As potency and capacity to induce double cut, they rank among the best simple enediyne analogues ever prepared. A thorough investigation was carried out in order to develop the best suited linkers for assembling these conjugates.
Boronic ester and acid compounds, synthesis and uses
-
, (2008/06/13)
Disclosed herein are boronic ester and acid compounds, their synthesis and uses. More specifically, disclosed herein is a method for reducing the rate of degradation of proteins in an animal comprising contacting cells of the animal with certain boronic ester and acid compounds.
Rhodium(II)-Catalyzed Decomposition of 1-Diazo-4-(1- or 2-naphthyl)-2-butanones as a New Route to Rearranged Pimarane and Abietane Skeleta. Synthesis of Umbrosone
Manitto, Paolo,Monti, Diego,Zanzola, Simona,Speranza, Giovanna
, p. 6658 - 6665 (2007/10/03)
The Rh2(OAc)4catalyzed intramolecular Buchner reaction of 1-diazo-4-(1- or 2-naphthyl)butan-2-ones was examined as a potential route to abietane and rearranged abietane derivatives. Treatment of the α-diazo ketone 26 with catalytic amount of dirhodium tetraacetate in CH2Cl2 at 0 °C furnished the tetracyclic derivative 27 in good yield. Addition of TFA to 27 (in CH2Cl2) resulted in an acid-induced opening of the cyclopropane ring to give the 4a- and 10a-methyldihydrophenanthrenones 28 and 29 in nearly equal amounts. These compounds and their analogs appear to be suitable intermediates for the synthesis of diterpenoids containing aromatic A or C rings. When the diazo ketone 34 was decomposed under Rh(II) catalysis, a 10-methyldihydroanthracenone (i.e., 36) was obtained as the main product, besides minor amounts of the expected tetracyclic ketone 35. The extension of this result to the preparation of the methoxy-substituted dihydroanthracenone 39 (52% yield) was exploited in a new total synthesis of umbrosone (6), an unusual diterpenoid possessing a rearranged linear skeleton.
Probing the abilities of synthetically useful serine proteases to discriminate remote stereocenters. Chiral naphthyl aldehyde inhibitors
Lee, Taekyu,Jones, J. Bryan
, p. 10260 - 10268 (2007/10/03)
The capacities of subtilisin Carlsberg (SC) and α-chymotrypsin (CT), which are representative of synthetically useful serine proteases, to discriminate between R- and S-configurations of stereocenters remote from the catalytic site have been further explo
Medetomidine analogs as α2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine
Zhang, Xiaoyan,Yao, Xiao-Tao,Dalton, James T.,Shams, Gamal,Lei, Longping,Patil, Popat N.,Feller, Dennis R.,Hsu, Fu-Lian,George, Cliff,Miller, Duane D.
, p. 3001 - 3013 (2007/10/03)
A new series of naphthalene analogs of medetomidine have been prepared and evaluated for their α-adrenergic activities. The methylnaphthyl analog 5a showed significant selectivity for α2-adrenoceptors and behaved as a partial α1-agonist in rat aorta preparations. In contrast, the Z-ethylene analog 8c was α1-selective and behaved as a potent α1-antagonist. Two rigid analogs (6 and 7) exhibited large differences in binding affinities at α1- vs α2-receptors, indicating that the conformational flexibility of 5a is important for the fulfillment of the α-adrenergic activities. Molecular modeling studies began with conformational analysis of classical phenethylamines and medetomidine analogs. Superimposition of medetomidine conformations with those of phenethylamines provided a tentative explanation for the α2-adrenergic activity of the new imidazoles. A common binding mode for phenethylamines and imidazoles with α2-adrenoceptors is proposed. Knowledge of the biological properties of the 4-substituted imidazoles, integrated with the information derived from computer-assisted molecular modeling, has provided new insights for the structural and conformational requirements of this class as new adrenergic drugs.
