- Biphenyl compound as well as preparation method and medical application thereof
-
The invention discloses a biphenyl compound as well as a preparation method and medical application thereof, the structure of the biphenyl compound is shown as a formula (I) or a formula (II), and thebiphenyl compound or pharmaceutically acceptable salt, tautomer, meso-isomer, raceme, stereoisomer, metabolite, metabolite precursor, prodrug or solvate thereof is a PD-L1 inhibitor. The compound hasa remarkable inhibiting effect on the interaction of PD-1 and PD-L1 protein, so that the compound can be applied to the preparation of PD-L1 inhibitors and immunomodulator drugs for preventing or treating tumors, autoimmune diseases, organ transplant rejection, infectious diseases and inflammatory diseases.
- -
-
Paragraph 1134-1140; 1155-0060
(2020/11/22)
-
- Para-Selective C-H Borylation of Common Arene Building Blocks Enabled by Ion-Pairing with a Bulky Countercation
-
The selective functionalization of C-H bonds at the arene para position is highly challenging using transition metal catalysis. Iridium-catalyzed borylation has emerged as a leading technique for arene functionalization, but there are only a handful of strategies for para-selective borylation, which operate on specific substrate classes and use bespoke ligands or catalysts. We describe a remarkably general protocol which results in para-selectivity on some of the most common arene building blocks (anilines, benzylamines, phenols, benzyl alcohols) and uses standard borylation ligands. Our strategy hinges upon the facile conversion of the substrates into sulfate or sulfamate salts, wherein the anionic arene component is paired with a tetrabutylammonium cation. We hypothesize that the bulk of this cation disfavors meta-C-H borylation, thereby promoting the challenging para-selective reaction.
- Mihai, Madalina T.,Williams, Benjamin D.,Phipps, Robert J.
-
supporting information
p. 15477 - 15482
(2019/10/11)
-
- Para-Selective, Iridium-Catalyzed C-H Borylations of Sulfated Phenols, Benzyl Alcohols, and Anilines Directed by Ion-Pair Electrostatic Interactions
-
Para C-H borylations (CHB) of tetraalkylammonium sulfates and sulfamates have been achieved using bipyridine-ligated Ir boryl catalysts. Selectivities can be modulated by both the length of the alkyl groups in the tetraalkylammonium cations and the substituents on the bipyridine ligands. Ion pairing, where the alkyl groups of the cation shield the meta C-H bonds in the counteranions, is proposed to account for para selectivity. The 4,4′-dimethoxy-2,2′-bipyridine ligand gave superior selectivities.
- Montero Bastidas, Jose R.,Oleskey, Thomas J.,Miller, Susanne L.,Smith, Milton R.,Maleczka, Robert E.
-
p. 15483 - 15487
(2019/10/11)
-
- Ir-Catalyzed ortho-Borylation of Phenols Directed by Substrate-Ligand Electrostatic Interactions: A Combined Experimental/in Silico Strategy for Optimizing Weak Interactions
-
A strategy for affecting ortho versus meta/para selectivity in Ir-catalyzed C-H borylations (CHBs) of phenols is described. From selectivity observations with ArylOBpin (pin = pinacolate), it is hypothesized that an electrostatic interaction between the partial negatively charged OBpin group and the partial positively charged bipyridine ligand of the catalyst favors ortho selectivity. Experimental and computational studies designed to test this hypothesis support it. From further computational work a second generation, in silico designed catalyst emerged, where replacing Bpin with Beg (eg = ethylene glycolate) was predicted to significantly improve ortho selectivity. Experimentally, reactions employing B2eg2 gave ortho selectivities > 99%. Adding triethylamine significantly improved conversions. This ligand-substrate electrostatic interaction provides a unique control element for selective C-H functionalization.
- Chattopadhyay, Buddhadeb,Dannatt, Jonathan E.,Andujar-De Sanctis, Ivonne L.,Gore, Kristin A.,Maleczka, Robert E.,Singleton, Daniel A.,Smith, Milton R.
-
p. 7864 - 7871
(2017/06/20)
-
- Preparation method of (3-(3-(dimethylamino) propoxy) phenyl) boronic acid
-
The invention discloses a preparation method of (3-(3-(dimethylamino) propoxy) phenyl) boronic acid. The preparation method comprises the following steps: (1) with 3-hydroxybenzeneboronic acid as a starting material, performing an esterification reaction
- -
-
Paragraph 0035; 0036
(2017/10/10)
-
- PHOSPHOINOSITIDE 3-KINASE INHIBITORS WITH ZINC BINDING MOIETY
-
PROBLEM TO BE SOLVED: To provide phosphoinositide 3-kinase inhibitors with a zinc binding moiety. SOLUTION: There is provided a compound represented by formula (I) in the figure. (X is S, O or the like; Y is CH, N or the like; G1 is optionally substituted N or the like; R1 and R2 are each independently H or the like; C is a substituted heterocycle or the like; B is a linear alkyl or the like; Ra and Rb together with the nitrogen atom coupled to them are morpholino or the like; G2 is an indazole ring or the like; q, r and s are independently from 0 to 1, provided that at least one of them is 1; t is from 0 to 1; n is from 0 to 4; and p is from 0 to 2.) COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 0296; 0337
(2016/10/07)
-
- SiliaCat diphenylphosphine palladium(II) catalyzed borylation of aryl halides
-
We investigate the heterogeneously catalyzed direct synthesis of boronic acid pinacol esters using a wide range of aryl chlorides, bromides, and iodides, and bis(pinacolato)diboron as the borylating agent over the sol-gel entrapped SiliaCat diphenylphosphine palladium(II) catalyst. Optimization of the reaction conditions, scale-up of the optimized process, and analysis of palladium leaching enabled us to establish a new selective route for direct access to a diverse set of boronic acid pinacol esters. Clean borylation for scale-up: With the easy access and broad availability of diverse borylated species, the Suzuki-Miyaura reaction has become routine in industry and in research labs. We report a new selective route for direct access to a diverse set of boronic acid pinacol esters over the sol-gel entrapped SiliaCat diphenylphosphine palladium(II) catalyst that can be easily scaled-up.
- Pandarus, Valerica,Marion, Olivier,Gingras, Genevieve,Beland, Francois,Ciriminna, Rosaria,Pagliaro, Mario
-
p. 1340 - 1348
(2014/05/20)
-
- Clean and fast cross-coupling of aryl halides in one-pot
-
Unsymmetrically coupled biaryls are synthesized in high yield starting from different aryl bromides and bis(pinacolato)diboron by carrying out the Miyaura borylation reaction followed by the Suzuki-Miyaura reaction in the same reaction pot over 1-2 mol % SiliaCat DPP-Pd. The SiliaCat DPP-Pd catalyst is air-stable and the method does not require the use of inert conditions. The use of non-toxic isopropanol or 2-butanol as reaction solvent further adds to the environmental benefits of this new green synthetic methodology.
- Pandarus, Valerica,Gingras, Genevieve,Beland, Francois,Ciriminna, Rosaria,Pagliaro, Mario
-
p. 897 - 901
(2014/05/20)
-
- TREATMENT OF CANCERS HAVING K-RAS MUTATIONS
-
The present invention provides a method of treating a cancer associated with a K-ras mutation in a subject in need thereof. The method comprises the steps of: (1) identifying a subject with a cancer associated with a K-ras mutation; and (2) administering to the subject (i) an inhibitor of PI3 kinase and (ii) an HDAC inhibitor, wherein the PI3 kinase inhibitor and the HDAC inhibitor are administered in amounts which together are therapeutically effective.
- -
-
Paragraph 0386; 0387
(2013/05/08)
-
- TREATMENT OF CANCERS HAVING K-RAS MUTATIONS
-
The present invention provides a method of treating a cancer associated with a K- ras mutation in a subject in need thereof. The method comprises the steps of (1) identifying a subject with a cancer associated with a K-ras mutation; and (2) adminsiterign to the subject (i) an inhibitor of PI3 kinase and (ii) an HDAC inhibitor, wherein the PI3 kinase inhibitor and the HDAC inhibitor are administered in amounts which together are therapeutically effective.
- -
-
Page/Page column 182
(2011/11/01)
-
- Gold(iii)-catalyzed halogenation of aromatic boronates with N -halosuccinimides
-
Aromatic boronates bearing halogen substituents in the aromatic ring can be synthesized by AuCl3-catalyzed halogenations with N-halosuccinimides.
- Qiu, Di,Mo, Fanyang,Zheng, Zhitong,Zhang, Yan,Wang, Jianbo
-
supporting information; experimental part
p. 5474 - 5477
(2011/02/22)
-
- Compositions for oxidatively dyeing keratin fibers and methods for using such compositions
-
Compositions for dyeing keratin fibers comprise (a) at least one keratin dyeing compound selected from aromatic systems which comprise at least one boronic acid or boronic ester moiety and which are capable of forming upon oxidation a nucleophile or an electrophile, (b) at least one additional keratin dyeing compound selected from the group consisting of auxiliary developers and auxiliary couplers, and (c) a cosmetically suitable medium. Methods for oxidatively dyeing keratin fibers comprise the steps of applying such compositions in the presence of an oxidizing agent and rinsing the hair. A hair coloring product in kit form comprises a first separately packaged container comprising a composition as described above and a second separately packaged container comprising an oxidizing agent.
- -
-
Page/Page column 8
(2008/06/13)
-
- Hydroboronation process
-
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.
- -
-
Page column 47
(2010/02/05)
-
- Deprotection of pinacolyl boronate esters by transesterification with polystyrene-boronic acid
-
A mild, efficient method for the deprotection of pinacolyl organoboronate esters is described. Treatment of the organoboronate ester with excess polystyrene-boronic acid followed by filtration and evaporation of the solvent provides the corresponding organoboronic acid. Mild deprotection of pinacolyl boronate esters to the corresponding boronic acids was achieved in the presence of excess polystyrene-boronic acid via a transesterification process. The procedure allows for the cleavage of pinacolyl boronate esters in the presence of sensitive functional groups. Crown Copyright
- Pennington, Thomas E.,Kardiman, Cynantya,Hutton, Craig A.
-
p. 6657 - 6660
(2007/10/03)
-
