1374772-55-0Relevant academic research and scientific papers
Discovery and optimization of new benzimidazole- and benzoxazole-pyrimidone selective PI3Kβ inhibitors for the treatment of phosphatase and TENsin homologue (PTEN)-deficient cancers
Certal, Victor,Halley, Frank,Virone-Oddos, Angela,Delorme, Cécile,Karlsson, Andreas,Rak, Alexey,Thompson, Fabienne,Filoche-Rommé, Bruno,El-Ahmad, Youssef,Carry, Jean-Christophe,Abecassis, Pierre-Yves,Lejeune, Pascale,Vincent, Loic,Bonnevaux, Hélène,Nicolas, Jean-Paul,Bertrand, Thomas,Marquette, Jean-Pierre,Michot, Nadine,Benard, Tsiala,Below, Peter,Vade, Isabelle,Chatreaux, Fabienne,Lebourg, Gilles,Pilorge, Fabienne,Angouillant-Boniface, Odile,Louboutin, Audrey,Lengauer, Christoph,Schio, Laurent
, p. 4788 - 4805 (2012)
Most of the phosphoinositide-3 kinase (PI3K) kinase inhibitors currently in clinical trials for cancer treatment exhibit pan PI3K isoform profiles. Single PI3K isoforms differentially control tumorigenesis, and PI3Kβ has emerged as the isoform involved in the tumorigenicity of PTEN-deficient tumors. Herein we describe the discovery and optimization of a new series of benzimidazole- and benzoxazole-pyrimidones as small molecular mass PI3Kβ-selective inhibitors. Starting with compound 5 obtained from a one-pot reaction via a novel intermediate 1, medicinal chemistry optimization led to the discovery of compound 8, which showed a significant activity and selectivity for PI3Kβ and adequate in vitro pharmacokinetic properties. The X-ray costructure of compound 8 in PI3Kδ showed key interactions and structural features supporting the observed PI3Kβ isoform selectivity. Compound 8 achieved sustained target modulation and tumor growth delay at well tolerated doses when administered orally to SCID mice implanted with PTEN-deficient human tumor xenografts.
QUINOXALINE DERIVATIVES
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Page/Page column 50, (2021/07/24)
The present invention relates to compounds according to general formula (I), which act as modulators of the glucocorticoid receptor and can be used in the treatment and/or prophylaxis of disorders which are at least partially mediated by the glucocorticoid receptor.
FURTHER SUBSTITUTED TRIAZOLO QUINOXALINE DERIVATIVES
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Paragraph 0284-0286, (2020/02/08)
The present invention relates to compounds according to general formula (I) which act as modulators of the glucocorticoid receptor and can be used in the treatment and/or prophylaxis of disorders which are at least partially mediated by the glucocorticoid receptor.
HETEROCYCLIC COMPOUNDS USEFUL AS ANTI-BACTERIAL AGENTS AND METHOD FOR PRODUCTION
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Paragraph 000197; 000198, (2017/12/15)
The present disclosure relates to compounds of Formula I, its stereoisomers, pharmaceutically acceptable salts, complexes, hydrates, solvates, tautomers, polymorphs, racemic mixtures, optically active forms thereof and pharmaceutical compositions containing them as the active ingredient which can be used as medicaments. The aforementioned substances can also be used in the manufacture of medicaments for treatment, prevention or suppression of diseases, and conditions mediated by microbes. The present disclosure also relates to the synthesis.and characterization of aforementioned substances.
