6237-17-8Relevant academic research and scientific papers
COMPOUNDS AND USES THEREOF
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Page/Page column 97, (2021/08/06)
The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
Novel, Self-Assembling Dimeric Inhibitors of Human β Tryptase
Giardina, Sarah F.,Werner, Douglas S.,Pingle, Maneesh,Feinberg, Philip B.,Foreman, Kenneth W.,Bergstrom, Donald E.,Arnold, Lee D.,Barany, Francis
, p. 3004 - 3027 (2020/04/17)
β-Tryptase, a homotetrameric serine protease, has four identical active sites facing a central pore, presenting an optimized setting for the rational design of bivalent inhibitors that bridge two adjacent sites. Using diol, hydroxymethyl phenols or benzoyl methyl hydroxamates, and boronic acid chemistries to reversibly join two [3-(1-acylpiperidin-4-yl)phenyl]methanamine core ligands, we have successfully produced a series of self-assembling heterodimeric inhibitors. These heterodimeric tryptase inhibitors demonstrate superior activity compared to monomeric modes of inhibition. X-ray crystallography validated the dimeric mechanism of inhibition, and compounds demonstrated high selectivity against related proteases, good target engagement, and tryptase inhibition in HMC1 xenograft models. Screening 3872 possible combinations from 44 boronic acid and 88 diol derivatives revealed several combinations that produced nanomolar inhibition, and seven unique pairs produced greater than 100-fold improvement in potency over monomeric inhibition. These heterodimeric tryptase inhibitors demonstrate the power of target-driven combinatorial chemistry to deliver bivalent drugs in a small molecule form.
2-CYANOISOINDOLINE DERIVATIVES FOR TREATING CANCER
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Page/Page column 77; 111, (2017/10/11)
The invention relates to novel compounds of formula I which are inhibitors of deubiquitylating enzymes (DUBs) and/or desumoylating enzymes. In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 7 or ubiquitin specific peptidase 7 (USP7). The invention further relates to methods for the preparation of these compounds and to their use in the treatment of cancer.
p38α mitogen-activated protein kinase inhibitors: Optimization of a series of biphenylamides to give a molecule suitable for clinical progression
Aston, Nicola M.,Bamborough, Paul,Buckton, Jacqueline B.,Edwards, Christopher D.,Holmes, Duncan S.,Jones, Katherine L.,Patel, Vipulkumar K.,Smee, Penny A.,Somers, Donald O.,Vitulli, Giovanni,Walker, Ann L.
experimental part, p. 6257 - 6269 (2010/03/31)
p38α MAP kinase is a key anti-inflammatory target for rheumatoid arthritis, influencing biosynthesis of pro-inflammatory cytokines TNFα and IL-1β at a translational and transcriptional level. In this paper, we describe how we have optimized a series of no
4-(1-benzoylindol-3-yl)butyric acids and FK143: Novel nonsteroidal inhibitors of steroid 5α-reductase (II)
Sawada, Kozo,Okada, Satoshi,Golden, Patrick,Kayakiri, Natsuko,Sawada, Yuki,Hashimoto, Masashi,Tanaka, Hirokazu
, p. 481 - 491 (2007/10/03)
A novel series of indolebutyric acids with varying benzoyl substituents were synthesized to develop nonsteroidal inhibitors of steroid 5α-reductase. We previously reported the discovery of a novel nonsteroidal 5α-reductase inhibitor, FR119680, which had a
