Discovery of an Oral, Rule of 5 Compliant, Interleukin 17A Protein-Protein Interaction Modulator for the Potential Treatment of Psoriasis and Other Inflammatory Diseases was written by Andrews, Mark D.;Dack, Kevin N.;de Groot, Marcel J.;Lambert, Maja;Sennbro, Carl J.;Larsen, Mogens;Stahlhut, Martin. And the article was included in Journal of Medicinal Chemistry in 2022.COA of Formula: C8H10O2 This article mentions the following:
Interleukin 17A (IL-17A) was an interleukin cytokine whose dysregulation implicated in autoimmune disorders such as psoriasis and monoclonal antibodies against the IL-17A pathway were now well-established and very effective treatments. Overlap of early ligands led to a series of benzhydrylglycine-containing compounds I [R1 = C(O)N(Me)2, pyrazol-4-yl, 3,5-(Me)2-pyrazol-4-yl, etc.; R2 = cyclopropyl, cyclohexyl, Ph, etc.; R3 = H, cyclopropyl Ph, etc.; R2R3 = Ph, cyclohexyl, cycloheptyl, etc.; R4 = Me, Et, iPr] that allowed foridentifying dimethylpyrazole as a key substituent that gave moderately potent PPIm with good oral bioavailability. Finally, optimization of the terminal amide group led to the identification of PPIm I [R1 = 3,5-(Me)2-pyrazol-4-yl; R2 = cyclopropyl; R3 = cyclopropyl; R4 = iPr] as a clin. development candidate with the potential to be an oral treatment of IL-17A-mediated diseases. Protein crystallog. provided knowledge of the key binding interactions between small-mol. ligands and the IL-17A dimer and this helped in the multiparameter optimization toward identifying an orally bioavailable, Rule of 5 compliant PPIm of IL-17A. Exploration of the amino acid portion of the structure then led to dicyclopropylalanine as a group that gave potent and metabolically stable compounds, including the development candidate I [R1 = 3,5-(Me)2-pyrazol-4-yl; R2 = cyclopropyl; R3 = cyclopropyl; R4 = iPr]. In the experiment, the researchers used many compounds, for example, (4-Methoxyphenyl)methanol (cas: 105-13-5COA of Formula: C8H10O2).
(4-Methoxyphenyl)methanol (cas: 105-13-5) belongs to ethers. Ethers are good solvents partly because they are not very reactive. Most ethers can be cleaved, however, by hydrobromic acid (HBr) to give alkyl bromides or by hydroiodic acid (HI) to give alkyl iodides. Ethyl ether is an excellent solvent for extractions and for a wide variety of chemical reactions. It is also used as a volatile starting fluid for diesel engines and gasoline engines in cold weather. Dimethyl ether is used as a spray propellant and refrigerant. Methyl t-butyl ether (MTBE) is a gasoline additive that boosts the octane number and reduces the amount of nitrogen-oxide pollutants in the exhaust. The ethers of ethylene glycol are used as solvents and plasticizers.COA of Formula: C8H10O2
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem