Discovery of a 1-Methyl-3,4-dihydronaphthalene-Based Sphingosine-1-Phosphate (S1P) Receptor Agonist Ceralifimod (ONO-4641). A S1P1 and S1P5 Selective Agonist for the Treatment of Autoimmune Diseases was written by Kurata, Haruto;Kusumi, Kensuke;Otsuki, Kazuhiro;Suzuki, Ryo;Kurono, Masakuni;Komiya, Takaki;Hagiya, Hiroshi;Mizuno, Hirotaka;Shioya, Hiroki;Ono, Takeji;Takada, Yuka;Maeda, Tatsuo;Matsunaga, Norikazu;Kondo, Tetsu;Tominaga, Sachiko;Nunoya, Ken-ici;Kiyoshi, Hidekazu;Komeno, Masaharu;Nakade, Shinji;Habashita, Hiromu. And the article was included in Journal of Medicinal Chemistry in 2017.Category: esters-buliding-blocks This article mentions the following:
The discovery of 1-({6-[(2-methoxy-4-propylbenzyl)oxy]-1-methyl-3,4-dihydronaphthalen-2-yl}methyl)azetidine3-carboxylic acid (I) (13n, ceralifimod, ONO-4641), a sphingosine-1-phosphate (S1P) receptor agonist selective for S1P1 and S1P5, is described. While it has been revealed that the modulation of the S1P1 receptor is an effective way to treat autoimmune diseases such as relapsing-remitting multiple sclerosis (RRMS), it was also reported that activation of the S1P3 receptor is implicated in some undesirable effects. The authors carried out a structure-activity relationship (SAR) study of hit compound 6 with an amino acid moiety in the hydrophilic head region. Following identification of a lead compound with a dihydronaphthalene central core by inducing conformational constraint, optimization of the lipophilic tail region led to the discovery of I as a clin. candidate that exhibited >30 000-fold selectivity for S1P1 over S1P3 and was potent in a peripheral lymphocyte lowering (PLL) test in mice (ED50 = 0.029 mg/kg, 24 h after oral dosing). In the experiment, the researchers used many compounds, for example, Methyl 2-methoxy-4-methylbenzoate (cas: 81245-24-1Category: esters-buliding-blocks).
Methyl 2-methoxy-4-methylbenzoate (cas: 81245-24-1) belongs to esters. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Category: esters-buliding-blocks
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics