- Glycan-Directed Grafting-from Polymerization of Immunoglobulin G: Site-Selectively Modified IgG-Polymer Conjugates with Preserved Biological Activity
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Antibody and related antibody drugs for the treatment of malignancies have led to progress in targeted cancer therapy. Preparation of diverse antibody conjugates is critical for preclinical and clinical applications. However, precise control in tagging molecules at specific locations on antibodies is essential to preserve their native function. In this study, a synthetic boronic acid (BA)-tosyl initiator was used to trigger a glycan-directed modification of IgGs, and the obtained IgG macroinitiators allowed a growth of the poly N-isopropylacrylamide (PNIPAAm) chains specifically at Fc-domains. Therefore, the PNIPAAm chains are located away from the critical antigen-binding domains (Fab), which could reasonably prevent the loss of biological activity after the attachment of polymer chains. According to the proposed strategy, a site-selectively modified anticoncanavalin A (Con A) antibody-PNIPAAm conjugate showed 6-times higher efficiency in the binding of targeted Con A antigen to a randomly conjugated anti-Con A antibody-PNIPAAm conjugate. In this study, we developed the first chemical strategy for the site-specific preparation of IgG-polymer conjugates with conserved biological activity as well as intact glycan structures.
- Chou, Chih-Hung,Lin, Po-Chiao
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Read Online
- Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton's Tyrosine Kinase (BTK)
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Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fc receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clinical studies.
- Watterson, Scott H.,Liu, Qingjie,Beaudoin Bertrand, Myra,Batt, Douglas G.,Li, Ling,Pattoli, Mark A.,Skala, Stacey,Cheng, Lihong,Obermeier, Mary T.,Moore, Robin,Yang, Zheng,Vickery, Rodney,Elzinga, Paul A.,Discenza, Lorell,D'Arienzo, Celia,Gillooly, Kathleen M.,Taylor, Tracy L.,Pulicicchio, Claudine,Zhang, Yifan,Heimrich, Elizabeth,McIntyre, Kim W.,Ruan, Qian,Westhouse, Richard A.,Catlett, Ian M.,Zheng, Naiyu,Chaudhry, Charu,Dai, Jun,Galella, Michael A.,Tebben, Andrew J.,Pokross, Matt,Li, Jianqing,Zhao, Rulin,Smith, Daniel,Rampulla, Richard,Allentoff, Alban,Wallace, Michael A.,Mathur, Arvind,Salter-Cid, Luisa,Macor, John E.,Carter, Percy H.,Fura, Aberra,Burke, James R.,Tino, Joseph A.
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Read Online
- Tuning the sugar-response of boronic acid block copolymers
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A detailed study of the pH- and sugar-responsive behavior of poly(3-acrylamidophenylboronic acid pinacol ester)-b-poly(N,N- dimethylacrylamide) (PAPBAE-b-PDMA) block copolymers is presented. Reversible addition-fragmentation chain transfer (RAFT) polymerization of the pinacol ester of 3-acrylamidophenylboronic acid resulted in homopolymers with molecular weights between 12,000 and 37,000 g/mol. The resulting homopolymers were employed as macro-chain transfer agents during the polymerization of N,N-dimethylacrylamide (DMA). Successful chain extension and removal of the pinacol protecting groups to yield poly(3-acrylamidophenylboronic acid)-b-PDMA (PAPBA-b-PDMA) with free boronic acid moieties resulted in pH- and sugar-responsive block copolymers that were subsequently investigated for their behavior in aqueous solution. The PAPBA-b-PDMA block copolymers were capable of solution self-assembly due to the PAPBA block being water-insoluble below its pKa. The resulting aggregates were demonstrated to solubilize and release model hydrophobic compounds, as demonstrated by fluorescence studies. Dissociation of the aggregates was induced by raising the pH above the pK a of the boronic acid residues or by adding sugars capable of forming boronate esters. Aggregate size, dissociation kinetics, and the effect of various sugars were considered. The critical sugar concentration needed to induce aggregate dissociation was tuned by incorporation of hydrophilic DMA units within the PAPBA responsive segment to yield PDMA-b-poly(3- acrylamidophenylboronic acid-co-DMA) block copolymers.
- Cambre, Jennifer N.,Roy, Debashish,Sumerlin, Brent S.
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Read Online
- Water-Soluble Polymeric Probes for the pH-Tunable Fluorometric Detection of Hydrogen Peroxide
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Hydrogen peroxide (H2O2) is an important reactive oxygen species (ROS) that plays a significant role in many biological systems. A new water-soluble polymeric probe appended with pyrene and boronic acid groups was designed and synthesized for the detection of H2O2. Glycidyl methacrylate (GMA) and N,N-dimethylacrylamide (DMA) were copolymerized by reversible addition-fragmentation chain-transfer (RAFT) polymerization to yield poly(glycidyl methacrylate-co-dimethylacrylamide) [p(GMA-co-DMA)](P1). The subsequent ring-opening reaction between the secondary amine of (3-((pyren-1-ylmethyl)amino)phenyl)boronic acid with the epoxide unit of P1 yielded a target polymer, P2. In the presence of H2O2, the phenyl boronic acid group of P2 transformed to a phenol group, which was accompanied by turn-off fluorescence. P2 also exhibited pH-tunable detection sensitivity. This polymeric probe is anticipated to promote the development of stimuli-responsive water-soluble polymers with fluorescence-sensing behaviors.
- Annisa, Tiara Nur,Lee, Hyung-il
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Read Online
- Nickel-Catalyzed Ipso-Borylation of Silyloxyarenes via C-O Bond Activation
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The conversion of silyloxyarenes to boronic acid pinacol esters via nickel catalysis is described. In contrast to other borylation protocols of inert C-O bonds, the method is competent in activating the carbon-oxygen bond of silyloxyarenes in isolated aromatic systems lacking a directing group. The catalytic functionalization of benzyl silyl ethers was also achieved under these conditions. Sequential cross-coupling reactions were achieved by leveraging the orthogonal reactivity of silyloxyarenes, which could then be functionalized subsequently.
- Pein, Wesley L.,Wiensch, Eric M.,Montgomery, John
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supporting information
(2021/06/28)
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- Photo-induced thiolate catalytic activation of inert Caryl-hetero bonds for radical borylation
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Substantial effort is currently being devoted to obtaining photoredox catalysts with high redox power. Yet, it remains challenging to apply the currently established methods to the activation of bonds with high bond dissociation energy and to substrates with high reduction potentials. Herein, we introduce a novel photocatalytic strategy for the activation of inert substituted arenes for aryl borylation by using thiolate as a catalyst. This catalytic system exhibits strong reducing ability and engages non-activated Caryl–F, Caryl–X, Caryl–O, Caryl–N, and Caryl–S bonds in productive radical borylation reactions, thus expanding the available aryl radical precursor scope. Despite its high reducing power, the method has a broad substrate scope and good functional-group tolerance. Spectroscopic investigations and control experiments suggest the formation of a charge-transfer complex as the key step to activate the substrates.
- K?nig, Burkhard,Wang, Hua,Wang, Shun
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supporting information
p. 1653 - 1665
(2021/06/17)
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- Development and Application of Efficient Ag-based Hydrogenation Catalysts Prepared from Rice Husk Waste
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The development of strategies for the sustainable management and valorization of agricultural waste is of outmost importance. With this in mind, we report the use of rice husk (RH) as feedstock for the preparation of heterogeneous catalysts for hydrogenation reactions. The catalysts were prepared by impregnating the milled RH with a silver nitrate solution followed by carbothermal reduction. The composition and morphology of the prepared catalysts were fully assessed by IR, AAS, ICP-MS, XPS, XRD and STEM techniques. This novel bio-genic silver-based catalysts showed excellent activity and remarkable selectivity in the hydrogenation of nitro groups in both aromatic and aliphatic substrates, even in the presence of reactive functionalities like halogens, carbonyls, borate esters or nitriles. Recycling experiments showed that the catalysts can be easily recovered and reused multiple times without significant drop in performance and without requiring re-activation.
- Unglaube, Felix,Kreyenschulte, Carsten Robert,Mejía, Esteban
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p. 2583 - 2591
(2021/04/09)
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- Visible Light-Induced Borylation of C-O, C-N, and C-X Bonds
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Boronic acids are centrally important functional motifs and synthetic precursors. Visible light-induced borylation may provide access to structurally diverse boronates, but a broadly efficient photocatalytic borylation method that can effect borylation of a wide range of substrates, including strong C-O bonds, remains elusive. Herein, we report a general, metal-free visible light-induced photocatalytic borylation platform that enables borylation of electron-rich derivatives of phenols and anilines, chloroarenes, as well as other haloarenes. The reaction exhibits excellent functional group tolerance, as demonstrated by the borylation of a range of structurally complex substrates. Remarkably, the reaction is catalyzed by phenothiazine, a simple organic photocatalyst with MW 200 that mediates the previously unachievable visible light-induced single electron reduction of phenol derivatives with reduction potentials as negative as approximately - 3 V versus SCE by a proton-coupled electron transfer mechanism. Mechanistic studies point to the crucial role of the photocatalyst-base interaction.
- Arman, Hadi D.,Dang, Hang. T.,Haug, Graham C.,He, Ru,Jin, Shengfei,Larionov, Oleg V.,Nguyen, Viet D.,Nguyen, Vu T.,Schanze, Kirk S.
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supporting information
(2020/02/04)
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- Discovery of a novel class of covalent dual inhibitors targeting the protein kinases bmx and btk
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The nonreceptor tyrosine TEC kinases are key regulators of the immune system and play a crucial role in the pathogenesis of diverse hematological malignancies. In contrast to the substantial efforts in inhibitor development for Bruton’s tyrosine kinase (BTK), specific inhibitors of the other TEC kinases, including the bone marrow tyrosine kinase on chromosome X (BMX), remain sparse. Here we present a novel class of dual BMX/BTK inhibitors, which were designed from irreversible inhibitors of Janus kinase (JAK) 3 targeting a cysteine located within the solvent-exposed front region of the ATP binding pocket. Structure-guided design exploiting the differences in the gatekeeper residues enabled the achievement of high selectivity over JAK3 and certain other kinases harboring a sterically demanding residue at this position. The most active compounds inhibited BMX and BTK with apparent IC50 values in the single digit nanomolar range or below showing moderate selectivity within the TEC family and potent cellular target engagement. These compounds represent an important first step towards selective chemical probes for the protein kinase BMX.
- Forster, Michael,Liang, Xiaojun Julia,Schr?der, Martin,Gerstenecker, Stefan,Chaikuad, Apirat,Knapp, Stefan,Laufer, Stefan,Gehringer, Matthias
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- Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton's Tyrosine Kinase (BTK)
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Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fc receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clinical studies.
- Watterson, Scott H.,Liu, Qingjie,Beaudoin Bertrand, Myra,Batt, Douglas G.,Li, Ling,Pattoli, Mark A.,Skala, Stacey,Cheng, Lihong,Obermeier, Mary T.,Moore, Robin,Yang, Zheng,Vickery, Rodney,Elzinga, Paul A.,Discenza, Lorell,D'Arienzo, Celia,Gillooly, Kathleen M.,Taylor, Tracy L.,Pulicicchio, Claudine,Zhang, Yifan,Heimrich, Elizabeth,McIntyre, Kim W.,Ruan, Qian,Westhouse, Richard A.,Catlett, Ian M.,Zheng, Naiyu,Chaudhry, Charu,Dai, Jun,Galella, Michael A.,Tebben, Andrew J.,Pokross, Matt,Li, Jianqing,Zhao, Rulin,Smith, Daniel,Rampulla, Richard,Allentoff, Alban,Wallace, Michael A.,Mathur, Arvind,Salter-Cid, Luisa,Macor, John E.,Carter, Percy H.,Fura, Aberra,Burke, James R.,Tino, Joseph A.
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p. 3228 - 3250
(2019/04/17)
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- GLUCOCORTICOID RECEPTOR AGONIST AND IMMUNOCONJUGATES THEREOF
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Provided herein are glucocorticoid receptor agonist immunoconjugates, glucocorticoid receptor agonists, and methods of using the same.
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Paragraph 00135-0136
(2019/06/14)
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- ANTI-CD40 ANTIBODY DRUG CONJUGATES
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Provided herein are anti-CD40 antibody drug conjugates comprising a radical of Formula (I), wherein R1, R2, and R3 are as defined herein. Further provided are anti-CD40 antibody drug conjugates of Formula (II), wherein Z, R, AA1, AA2, AA3, m, p, q, n, w, R1, R2, and R3 are as defined herein. Further provided are pharmaceutical compositions and kits thereof, and methods of using same.
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Paragraph 00140
(2019/06/17)
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- Achieving High Ortho Selectivity in Aniline C-H Borylations by Modifying Boron Substituents
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High ortho selectivity for Ir-catalyzed C-H borylations (CHBs) of anilines results when B2eg2 (eg = ethylene glycolate) is used as the borylating reagent in lieu of B2pin2, which is known to give isomeric mixtures with anilines lacking a blocking group at the 4-position. With this modification, high selectivities and good yields are now possible for various anilines, including those with groups at the 2- and 3-positions. Experiments indicate that ArylN(H)Beg species are generated prior to CHB and support the improved ortho selectivity relative to B2pin2 reactions arising from smaller Beg ligands on the Ir catalyst. The lowest-energy transition states (TSs) from density functional theory computational analyses have N-H···O hydrogen-bonding interactions between PhN(H)Beg and O atoms in Beg ligands. Ir-catalyzed CHB of PhN(H)Me with B2eg2 is also highly ortho-selective. 1H NMR experiments show that N-borylation fully generates PhN(Me)Beg prior to CHB. The TS with the lowest Gibbs energy was the ortho TS, in which the Beg unit is oriented anti to the bipyridine ligand.
- Smith, Milton R.,Bisht, Ranjana,Haldar, Chabush,Pandey, Gajanan,Dannatt, Jonathan E.,Ghaffari, Behnaz,Maleczka, Robert E.,Chattopadhyay, Buddhadeb
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p. 6216 - 6223
(2018/05/23)
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- LiHMDS-Promoted Palladium or Iron-Catalyzed ipso-Defluoroborylation of Aryl Fluorides
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A novel and efficient method for the synthesis of arylboronic acid pinacol esters via a palladium- or iron-catalyzed cross-coupling reaction of aryl fluorides with bis(pinacolato)diboron (B2pin2) in the presence of LiHMDS was developed. The Pd-catalyzed defluoroborylation of fluoroarenes is compatible with a variety of functional groups such as primary and secondary amine, ketone, trifluoromethyl, alkoxy, and boryl. Remarkably, no external ligand is required for enhanced conversion efficiency.
- Zhao, Xianghu,Wu, Mingsheng,Liu, Yisen,Cao, Song
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supporting information
p. 5564 - 5568
(2018/09/12)
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- Discovery and evaluation of 3,5-disubstituted indole derivatives as Pim kinase inhibitors
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Pim kinases are promising therapeutic targets for the treatment of hematological cancers. A potent Pim kinase inhibitor 7f, derived from meridianin C, was further optimized by the replacement of 2-aminopyrimidine with substituted benzene. The optimization of the C-3 and C-5 positions of indole yielded compound 43 with improved cellular potency and high selectivity against a panel of 14 different kinases.
- More, Kunal N.,Hong, Victor S.,Lee, Ahyeon,Park, Jongsung,Kim, Shin,Lee, Jinho
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supporting information
p. 2513 - 2517
(2018/06/06)
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- Room-temperature borylation and one-pot two-step borylation/Suzuki-Miyaura cross-coupling reaction of aryl chlorides
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A highly efficient room-temperature borylation strategy of aryl chlorides is described. Utilizing Buchwald's second-generation preformed catalyst, boronate esters were obtained for a wide range of substrates in high yield. The method was also applied to Suzuki-Miyaura cross-coupling reaction in a one-pot two-step sequential manner, providing a facile and convenient access to the direct synthesis of biaryl compounds from aryl chlorides.
- Ji, Hong,Wu, Li-Yang,Cai, Jiang-Hong,Li, Guo-Rong,Gan, Na-Na,Wang, Zhao-Hua
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p. 13643 - 13648
(2018/04/24)
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- Photoinitiated long-lived charge separation with near-unity quantum yield in donor-acceptor1-acceptor2 systems for artificial photosynthesis
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We report the synthesis and photophysical characterization of isomeric donor-acceptor1-acceptor2 (D-A1-A2) triads each comprising a perylene donor (D) connected by a xylene bridge to a naphthalene-1,8-dicarboximide primary acceptor (NMI, A1) that is, in turn, covalently linked to a naphthalene-1,4:5,8-bis(dicarboximide) secondary acceptor (NDI, A2) through a benzene ring at its ortho, meta or para positions (Per-Xy-NMI-x-NDI). Selective photoexcitation of Per produces both Per+? and NDI?? simultaneously with time constants of ~50 ps in benzonitrile and ~80 ps in toluene with a >98% yield. This is much faster than expected for single-step electron transfer from 1*Per to NDI and is consistent with a two-step mechanism, 1*Per-Xy-NMI-x-NDI → Per+?-Xy-NMI??-x-NDI → Per+?-Xy-NMI-x-NDI??, in which the second step is much faster than the first step. In addition, preserving long-lived charge separation in these systems is found to depend on inhibiting charge recombination by a triplet radical ion pair recombination pathway.
- Han, Won-Sik,Veldkamp, Brad S.,Dyar, Scott M.,Eaton, Samuel W.,Wasielewski, Michael R.
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p. 4925 - 4935
(2017/07/27)
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- A synthetic amino acid frequency that alcohol ester
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The invention relates to a method of synthesizing aminophenylboronic acid pinacol ester. The method includes subjecting bromoaniline having different substitute positions to silanization protection, reacting with magnesium metal or butyl lithium, and performing boronization/deprotection/esterification to obtain a product. Raw materials and agents, which are adopted in the method, are cheap and easily available. Reaction conditions are mild. Only simple treatment is needed after a reaction in each step is finished. The method is capable of continuous operation. The total yield is 40-55%. The purity of the product is high. The method is suitable for large-scale amplification production.
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Paragraph 0042; 0043; 0044; 0045
(2017/08/25)
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- Radical Metal-Free Borylation of Aryl Iodides
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A simple metal-free borylation of aryl iodides mediated by a fluoride sp 2 -sp 3 diboron adduct is described. The reaction conditions are compatible with various functional groups. Electronic effects of substituents do not affect the borylation while steric hindrance does. The reaction proceeds via a radical mechanism in which pyridine serves to stabilize the boryl radicals, generated in situ.
- Pinet, Sandra,Liautard, Virginie,Debiais, Mégane,Pucheault, Mathieu
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p. 4759 - 4768
(2017/10/03)
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- GLUCOCORTICOID RECEPTOR AGONIST AND IMMUNOCONJUGATES THEREOF
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Provided herein are glucocorticoid receptor agonist immunoconjugates, glucocorticoid receptor agonists, and methods of using the same, e.g., to treat autoimmune or inflammatory diseases.
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Paragraph 00968; 00969; 00978; 00979
(2018/01/17)
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- CARBAZOLE DERIVATIVES
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Disclosed are compounds of Formula (I): (I) or a salt thereof, wherein Q, R1a, R1b, R2a, R2b, R3, R4, R5a, R5b, R6a, R6c, R7a, R7b, R7c, and R7d are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
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Page/Page column 108
(2016/05/24)
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- INDOLE CARBOXAMIDE COMPOUNDS
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Disclosed are compounds of Formula (I): or a salt thereof, wherein: X is CR4 or N; R1, R2, R3, R4, and A are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
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Paragraph 0503-0504
(2016/05/19)
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- Discovery of novel VEGFR-2 inhibitors. Part 5: Exploration of diverse hinge-binding fragments via core-refining approach
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Pathological angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. We have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to our previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, 12e and 12o displayed excellent VEGFR-2 inhibitory activity with IC50 values of 0.50 nM and 0.79 nM, respectively. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, molecular docking was performed to rationalize the efficiency of the better compounds. These results will be instructive for further inhibitor design and optimization.
- Shan, Yuanyuan,Gao, Hongping,Shao, Xiaowei,Wang, Jinfeng,Pan, Xiaoyan,Zhang, Jie
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- PROCESS FOR THE PREPARATION OF AMINOARYL- AND AMINOHETEROARYL BORONIC ACIDS AND ESTERS
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The present invention relates to a process for the preparation of aminoaryl- and aminoheteroaryl boronic acids and esters thereof of formula (I) in high yield. The claimed process uses diarylketal formula (V) to generate an arylbromide of formula (III) in which the amino-group is protected as bisarylmethylidenimino-group, which is then transformed into a formula (I) compound.
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Page/Page column 16
(2014/12/09)
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- Process for the preparation of aminoaryl- and aminoheteroaryl boronic acids and esters
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The present invention relates to a process for the preparation of aminoaryl- and aminoheteroaryl boronic acids and esters of formula (I) in high yields The claimed process uses diarylketal formula (V) to generate an arylbromid of formula (III) in which the amino-group is protected as bisarylmethylidenimino-group:
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- Synthesis of trimethylstannyl arylboronate compounds by sandmeyer-type transformations and their applications in chemoselective cross-coupling reactions
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A synthetic method based on Sandmeyer-type reactions to access both tin- and boron-substituted arenes from nitroaniline derivatives is described. This transformation can be applied to the synthesis of a series of functionalized trimethylstannyl arylboronates. In addition, the chemoselective reaction of the Stille and Suzuki-Miyaura cross-coupling reactions is explored, and a series of m- and p-terphenyl derivatives have been synthesized by conducting consecutive one-pot Stille and Suzuki-Miyaura cross-coupling reactions.
- Qiu, Di,Wang, Shuai,Tang, Shengbo,Meng, He,Jin, Liang,Mo, Fanyang,Zhang, Yan,Wang, Jianbo
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p. 1979 - 1988
(2014/04/03)
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- A traceless directing group for C - H borylation
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Not a trace: Borylation of the nitrogen in nitrogen heterocycles or anilines provides a traceless directing group for subsequent catalytic C - H borylation. Selectivities that previously required Boc protection can be achieved; furthermore, the NBpin directing group can be installed and removed in situ, and product yields are substantially higher. Boc=tert-butoxycarbonyl, pin=pinacolato. Copyright
- Preshlock, Sean M.,Plattner, Donald L.,Maligres, Peter E.,Krska, Shane W.,Maleczka Jr., Robert E.,Smith III, Milton R.
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supporting information
p. 12915 - 12919
(2014/01/06)
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- Palladium-catalyzed borylation of aryl mesylates and tosylates and their applications in one-pot sequential suzuki-miyaura biaryl synthesis
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Top of the one-pots! The first palladium-catalyzed borylation of aryl tosylates and mesylates is described. The reaction conditions are mild and provide excellent functional-group compatibility (e.g., R=CN, CHO, COOMe, C(O)R, NH2, or NH-indole; see scheme). Pd/MeO-CM-phos allows one-pot sequential reactions in the preparation of unsymmetrical biaryls. Copyright
- Chow, Wing Kin,So, Chau Ming,Lau, Chak Po,Kwong, Fuk Yee
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p. 6913 - 6917
(2011/08/03)
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- PXPd-catalyzed borylation of aniline derivatives
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Addition of pinacolborane (HBO2C2Me4) to 2-iodoaniline can be catalyzed using a number of palladium complexes, including [(t-Bu)2PCl]2PdCl2 (PXPd), to give the corresponding boronate ester 2-H2NC6H4(BO2C2Me4) in excellent yields. The PXPd system could also be used in the catalyzed borylation of substituted anilines to give the corresponding aminoboronate esters in moderate to high yields.
- Wheaton, Susan L.,Kabir, S.M. Humanayun,Zhang, Haiwen,Vogels, Christopher M.,Decken, Andreas,Westcott, Stephen A.
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experimental part
p. 725 - 731
(2011/11/04)
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- Cyclopalladated ferrocenylimine as efficient catalyst for the syntheses of arylboronate esters
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The cyclopalladated ferrocenylimine I and its phosphine adducts IIa-f were prepared and evaluated in the borylation of aryl halides. The tricyclohexylphosphine adduct IIb exhibited highly catalytic activity for the coupling of aryl and heteroaryl bromides containing various functional groups with low catalyst loading (2 mol%). Aryl and heteroaryl chlorides were smoothly converted into the corresponding boronates in the presence of the monophosphinobiaryl ligand (XPhos) adduct IIf. It was proposed that palladacycle was only a reservoir of the catalytically active species from the investigation on the reaction mechanism.
- Wang, Lianhui,Li, Jingya,Cui, Xiuling,Wu, Yusheng,Zhu, Zhiwu,Wu, Yangjie
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experimental part
p. 2002 - 2010
(2010/10/19)
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- Preparation of Aminoaryl and Aminoheteroaryl Boronic Acids and Derivatives Thereof
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The invention relates to a method for preparation of aminoaryl- or aminoheteroarylboronic acids and esters and salts thereof in which an optionally substituted aminoaryl or aminoheteroaryl compound is protected at its nitrogen site via condensation with a carbonyl compound, subsequently metalated and converted with a suitable boron compound. Depending on the subsequent work-up and removal of the protective group, the corresponding boronic acid, the anhydride or the boronic acid ester thereof is obtained
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Page/Page column 5
(2008/12/04)
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- Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhbitors
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The present invention relates to 8-amino-aryl-substituted imidazopyrazines which modulate the activity of protein kinases (“PKs”). The compounds of this invention are therefore useful in treating disorders related to abnormal PK activity. Pharmaceutical compositions comprising these compounds, methods of treating diseases utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.
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- Palladium-catalyzed borylation of phenyl bromides and application in one-pot Suzuki-Miyaura biphenyl synthesis
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(Chemical equation presented) The coupling reaction of pinacolborane with various aryl bromides in the presence of a catalytic amount of Pd(OAc) 2 together with DPEphos as ligand and Et3N as base provided arylboronates. High yields were obtained in the case of electron-donor substituted aryl bromides. The direct preparation of arylboronates allowed the one-pot, two-step synthesis of unsymmetrical biaryls in high yields.
- Broutin, Pierre-Emmanuel,Cerna, Igor,Campaniello, Maria,Leroux, Frederic,Colobert, Francoise
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p. 4419 - 4422
(2007/10/03)
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- Hydroboronation process
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The invention relates to processes for the synthesis of aryl or alkene borates which comprises reacting: (i) an olefinic compound having a halogen or halogen-like substituent in a vinylic substitution position, or (ii) an aromatic ring having a halogen or halogen-like substituent in a ring substitution position, with a disubstituted monohydroborane in the presence of a Group 8-11 metal catalyst. The invention also relates to the use of these borates in coupling reactions. The invention further relates to certain disubstituted monohydroboranes and aryl or alkene borates.
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Page column 72
(2010/02/05)
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- Sulfonamide derivatives
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The present invention provides certain sulfonamide derivatives useful for potentiating glutamate receptor function in a patient and therefore, useful for treating a wide variety of conditions, such as psychiatric and neurological disorders.
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- Reactions of aminoboron compounds with palladium and platinum complexes
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Reactions of 3-NH2C6H4B(OH)2 (1, APBA) with [MCl4]2- (M = Pd, Pt) give the boronic acid-containing complexes, MCl2(APBA)2 (M = Pd, 2; M = Pt, 3). Addition of 1 to [PdCl2(COE)]2 (COE = η2-C8H14) ultimately led to PdCl2(APBA)2 (2). The pinacol derivative PdCl2(APBpin)2 (5, pin = O2C2Me4) was characterized by an X-ray diffraction study. Crystals of 5 were monoclinic, a = 13.836(5), b = 14.937(5), c = 11.287(5) A, β = 99.042(9)°, Z = 2, with space group P21/c. Monoalkene complexes PtCl2(COE)(APBA) (8) and PtCl2(COE)(APBpin) (9) were generated from the addition of APBA and APBpin, respectively, to [PtCl2(COE)]2. Reactions of 2-NMe2CH2C6H4B(OH)2 (10) with palladium complex [PdCl2(COE)]2 proceed via selective B - C bond cleavage to give the cyclopalladated dimer [PdCl(2-NMe2CH2C6H4)]2 as the major amine-containing product. Likewise, reactions with borinic esters H2NCH2CH2OBR2 (R = Bu, 14; R = Ph, 15) give products derived from cleavage of the B - O bond. The unique palladium complex PdCl2[S-NC5H4B(OH)2]2 (19) was prepared by addition of (3-NC5H4BEt2)4 (18) to [PdCl2(COE)]2 in wet methylene chloride, where adventitious water was used to convert the organoborane product into the corresponding boronic acid moiety.
- Vogels, Christopher M.,Wellwood, Heather L.,Biradha, Kumar,Zaworotko, Michael J.,Westcott, Stephen A.
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p. 1196 - 1207
(2007/10/03)
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