HPLC of Formula: 109-01-3In 2022 ,《Structural and PK-guided identification of indole-based non-acidic autotaxin (ATX) inhibitors exhibiting high in vivo anti-fibrosis efficacy in rodent model》 was published in European Journal of Medicinal Chemistry. The article was written by Lei, Hongrui; Cao, Zhi; Wu, Huinan; Li, Tong; Wang, Xinyu; Chen, Yuxiang; Ma, Enlong; Sun, Lixin; Zhai, Xin. The article contains the following contents:
In recent decades, pharmacol. targeting of the autotaxin (ATX)/lysophosphatidic acid (LPA) axis accounted for excellent disease management benefits. Herein, to extend the scope of structure-activity relationships (SARs), fifteen indole-based carbamate derivatives I [R = 4-Me, 3,4-difluoro, 2,3-dichloro; R1 = pyrrolidin-1-yl, (4-methyl-1-piperidyl), (4-methylpiperazin-1-yl); R2 = H, CH3, etc] were prepared to evaluate the ATX inhibitory potency. Among them, compound I [R = 3,5-dichloro; R1 = morpholino; R2 = H] bearing morpholine moiety was identified as the optimal ATX inhibitor (0.41 nM), superior to the pos. control GLPG1690 (2.90 nM). To resolve the intractable issue of poor pharmacokinetic (PK) property, urea moiety was introduced as a surrogate of carbamate which furnished compounds II [R3 = morpholino, (4-hydroxy-1-piperidyl), [2-(hydroxymethyl)pyrrolidin-1-yl]; R4 = H, 4-Cl, 4-F, etc]. The dedicated modification identified the diethanolamine entity II [R3 = [bis(2-hydroxyethyl)amino]; R4 = (3-chloro-4-methoxy-phenyl)] with satisfactory water solubility and PK profiles with a min. sacrifice of ATX inhibition (2.17 nM). The most promising candidate II [R3 = [bis(2-hydroxyethyl)amino]; R4 = (3-chloro-4-methoxy-phenyl)] was evaluated for anti-fibrosis effect in a bleomycin challenged mice lung fibrosis model. Upon treatment with II [R3 = [bis(2-hydroxyethyl)amino]; R4 = (3-chloro-4-methoxy-phenyl)], the in vivo ATX activity in both lung homogenate and broncheoalveolar fluid (BALF) sample was significantly down-regulated. Furthermore, the gene expression of pro-fibrotic cytokines transforming growth factor-β (TGF-β), interleukin- 6 (IL-6) and tumor necrosis factor-α (TNF-α) in lung tissue was reduced to normal level. Collectively, the promising biol. effects may advocate potential application of II [R3 = [bis(2-hydroxyethyl)amino]; R4 = (3-chloro-4-methoxy-phenyl)] in fibrosis relevant diseases. In the part of experimental materials, we found many familiar compounds, such as 1-Methylpiperazine(cas: 109-01-3HPLC of Formula: 109-01-3)
1-Methylpiperazine(cas: 109-01-3) can be used as mimic template in the preparation of molecularly imprinted microspheres (MIMs). It was also used to prepare the difunctional strong anion-exchange stationary phase from a 1,4-diazacyclohexane derivative..HPLC of Formula: 109-01-3
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics