500604-91-1

Upstream product

• 7311-63-9 5-bromothiophene-2-carboxylic acid 
• 3900-89-8 2-Chlorobenzeneboronic acid 
• 62224-19-5 5-bromo-2-thiophenecarboxylic acid methyl ester 
• 1024448-93-8 methyl 5-(2-chlorophenyl)thiophene-2-carboxylate 

Downstream Products

• 1332503-05-5 [5-(2-chlorophenyl)-2-thienyl]methanol 
• 1332503-09-9 2-(bromomethyl)-5-(2-chlorophenyl)thiophene 
• 1332501-93-5 5-(4-chlorophenyl)-2-{[5-(2-chlorophenyl)-2-thienyl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxy-propyl]-2,4-dihydro-3H-1,2,4-triazol-3-one 
• 500604-90-0 N-[(1S,2R,4R)-7-azabicyclo[2.2.1]hept-2-yl]-5-(2-chlorophenyl)thiophene-2-carboxamide Hydrochloride 

Relevant academic research and scientific papers

Broadening antifungal spectrum and improving metabolic stablity based on a scaffold strategy: Design, synthesis, and evaluation of novel 4-phenyl-4,5-dihydrooxazole derivatives as potent fungistatic and fungicidal reagents

5-phenylthiophene derivatives exhibited excellent antifungal activity against Candida albicans, Candida tropicalis and Cryptococcus neoformans. However, optimal compound 7 was inactive against Aspergillus fumigatus and unstable in human liver microsomes in vitro with a half-life of 18.6 min. To discover antifungal agents with a broad spectrum and improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of 4-phenyl-4,5-dihydrooxazole derivatives were designed and synthesized. It was especially encouraging that compound 22a displayed significant antifungal activities against eight susceptible strains and seven FLC-resistant strains. Furthermore, the potent compound 22a could prevent the formation of fungalbiofilms and displayed satisfactory fungicidal activity. In addition, the metabolic stability of compound 22a was improved significantly, with the half-life of 70.5 min. Compound 22a was almost nontoxic to mammalian A549, MCF-7, HepG2, and 293T cells. Moreover, pharmacokinetic studies in SD rats showed that compound 22a exhibited pharmacokinetic properties with a bioavailability of 15.22% and a half-life of 4.44 h, indicating that compound 22a is worthy of further study.

Synthesis and Biological Evaluation of B-Cell Lymphoma 6 Inhibitors of N-Phenyl-4-pyrimidinamine Derivatives Bearing Potent Activities against Tumor Growth

The transcriptional repressor B-cell lymphoma 6 (BCL6) is frequently misregulated in diffuse large B-cell lymphoma (DLBCL) and has emerged as an attractive drug target for the treatments of lymphoma. In this article, a series of N-phenyl-4-pyrimidinamine derivatives were designed and synthesized as potent BCL6 inhibitors by optimizing hit compound N4-(3-chloro-4-methoxyphenyl)-N2-isobutyl-5-fluoro-2,4-pyrimidinediamine on the basis of the structure-activity relationship. Among them, compound 14j displayed the most potent activities, which significantly blocked the interaction of BCL6 with its corepressors, reactivated BCL6 target genes in a dose-dependent manner, and had better effects compared with the two positive controls. Further studies indicated that a low dose of 14j could effectively inhibit germinal center formation. More importantly, 14j not only showed potent inhibition of DLBCL cell proliferation in vitro but also strongly suppressed the growth of DLBCL in vivo.

BISARYL-BONDED ARYLTRIAZOLONES AND USE THEREOF

The present application relates to novel bisaryl-linked 5-aryl-1,2,4-triazolone derivatives, to processes for preparing them, to their use alone or in combinations for the treatment and/or prevention of diseases and also to their use for the production of medicaments for the treatment and/or prevention of diseases, more particularly for the treatment and/or prevention of cardiovascular disorders.