106912-94-1Relevant articles and documents
Design, Synthesis, and Biological Evaluation of Imidazopyridines as PD-1/PD-L1 Antagonists
Butera, Roberto,Wa?yńska, Marta,Magiera-Mularz, Katarzyna,Plewka, Jacek,Musielak, Bogdan,Surmiak, Ewa,Sala, Dominik,Kitel, Radoslaw,De Bruyn, Marco,Nijman, Hans W.,Elsinga, Philip H.,Holak, Tad A.,D?mling, Alexander
, p. 768 - 773 (2021)
The PD-1/PD-L1 axis has proven to be a highly efficacious target for cancer immune checkpoint therapy with several approved antibodies. Also, small molecules based on a biphenyl core can antagonize PD-1/PD-L1, leading to the in vitro formation of PD-L1 dimers. However, their development remains challenging, as we do not yet fully understand their mode of action. In this work, we designed a new scaffold based on our previously solved high-resolution structures of low-molecular-weight inhibitors bound to PD-L1. A small compound library was synthesized using the Groebke-Blackburn-Bienaymé multicomponent reaction (GBB-3CR), resulting in the structure-activity relationship of imidazo[1,2-a]pyridine-based inhibitors. These inhibitors were tested for their biological activity using various biophysical assays giving potent candidates with low-micromolar PD-L1 affinities. An obtained PD-L1 cocrystal structure reveals the binding to PD-L1. Our results open the door to an interesting bioactive scaffold that could lead to a new class of PD-L1 antagonists.
Synthesis of Highly Substituted Phenols and Benzenes with Complete Regiochemical Control
Zhang, Xiaojie,Beaudry, Christopher M.
supporting information, p. 6086 - 6090 (2020/08/12)
Substituted phenols are requisite molecules for human health, agriculture, and diverse synthetic materials. We report a chemical synthesis of phenols, including penta-substituted phenols, that accommodates programmable substitution at any position. This method uses a one-step conversion of readily available hydroxypyrone and nitroalkene starting materials to give phenols with complete regiochemical control and in high chemical yield. Additionally, the phenols can be converted into highly and even fully substituted benzenes.
AROMATIC ACETYLENE OR AROMATIC ETHYLENE COMPOUND, INTERMEDIATE, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF
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Paragraph 0154; 0156, (2019/05/22)
Disclosed are an aromatic acetylene or aromatic ethylene compound, an intermediate, a preparation method, a pharmaceutical composition and a use thereof. The aromatic acetylene or aromatic ethylene compound has a significant inhibitory effect on PD-1 and PD-L1, and can effectively relieve or treat cancers and other related diseases.
3-(AZOLYLMETHOXY)BIPHENYL DERIVATIVES AS INHIBITORS OF THE PD-1/PD-L1 PROTEIN/PROTEIN INTERACTION
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Page/Page column 24; 25, (2019/01/22)
The present invention provides novel compounds of formula (I) that are useful as inhibitors of the PD-1/PD-L1 protein/protein interaction. The compounds may be used in the treatment of cancer, infectious diseases and neurodegenerative diseases such as schizophrenia, Alzheimer, multiple sclerosis or Parkinson.
HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS
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Paragraph 0474-0475, (2018/07/15)
Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds inhibit PD-1/PD-L1 interaction and are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.
Convenient Access to meta-Substituted Phenols by Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling and Oxidation
Wang, Zi,Orellana, Arturo
, p. 11445 - 11449 (2017/08/26)
We report a new approach to the synthesis of meta-substituted phenols in which a single palladium catalyst accomplishes a Suzuki–Miyaura cross-coupling between a β-chlorocyclohexenone and an arylboronic acid, and oxidation of the resulting cyclohexenone to the corresponding phenol upon introduction of a terminal oxidant and electron transfer mediator. Notably, this method also allows ready access to ortho, meta-disubstituted phenols, sterically congested biaryl phenols, and more highly substituted phenols.
INHIBITORS OF THE PD-1/PD-L1 PROTEIN/PROTEIN INTERACTION
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, (2017/08/01)
The present invention provides novel compounds of formula (I) that are useful as inhibitors of the PD-1/PD-L1 protein/protein interaction.
Pd-catalyzed modifiable silanol-directed aromatic C-H oxygenation
Huang, Chunhui,Ghavtadze, Nugzar,Godoi, Benhur,Gevorgyan, Vladimir
, p. 9789 - 9792 (2012/08/29)
Directing group: A Pd-catalyzed aromatic C-H oxygenation has been developed, featuring a modifiable silanol-directing group. The resulting oxasilacycles can be efficiently modified into a variety of valuable building blocks (see scheme). Copyright
Benzazepine formation by the 1.7 electrocyclisations of diene-conjugated nitrile ylides: studies on relative rates of cyclisation via intramolecular competition reactions
Cullen, Kevin E.,Sharp, John T.
, p. 2565 - 2580 (2007/10/02)
A series of reactions has been carried out using reactants of the type 19 in which nitrile ylide cyclisation on to the substituent at the 6 position is in competition with cyclisation on to the unsubstituted phenyl group at the 2 position.The relative reactivity of the two groups, determined by measuring the product ratio 20:21, was determined for a series of 6-substituents as shown in Table 8.This is the first collection of such data for the electrocyclisation of 1,3-dipolar intermediates.Alkenyl groups and the thiophene ring were found to be > 100 x more reactive than phenyl.In cases where the 6-substituent was a substituted aryl group it was found that all aromatic substituents at the 3' and 4' positions, irrespective of their electronic nature, increased the reactivity of the ring relative to that of the unsubstituted phenyl group.In contrast, a methyl group at the 2' position produced strong deactivation.The results are discussed in terms of the steric and electronic effects of the substituents.
A synthesis of highly substituted aromatics through regiocontrolled construction of cyclobutenones bearing unsaturated substituents at the 4-position
Krysan, Damian J.,Gurski, Angela,Liebeskind, Lanny S.
, p. 1412 - 1418 (2007/10/02)
2,3-Substituted 4-chloro-2-cyclobutenones, prepared by regiospecific transformations of substituted cyclobutenediones, undergo palladium-catalyzed cross-coupling with vinyl- and arylstannanes and vinylzirconium reagents to form 4-Runsat-2-cyclo
