Category: 65515-32-4

Structural Re-engineering of the 伪-Helix Mimetic JY-1-106 into Small Molecules: Disruption of the Mcl-1-Bak-BH3 Protein-Protein Interaction with 2,6-Di-Substituted Nicotinates was written by Drennen, Brandon;Scheenstra, Jacob A.;Yap, Jeremy L.;Chen, Lijia;Lanning, Maryanna E.;Roth, Braden M.;Wilder, Paul T.;Fletcher, Steven. And the article was included in ChemMedChem in 2016.Synthetic Route of C8H8ClNO3 This article mentions the following:

The disruption of aberrant protein-protein interactions (PPIs) with synthetic agents remains a challenging goal in contemporary medicinal chem. but some progress has been made. One such dysregulated PPI is that between the anti-apoptotic Bcl-2 proteins, including myeloid cell leukemia-1 (Mcl-1), and the 伪-helical Bcl-2 homol.-3 (BH3) domains of its pro-apoptotic counterparts, such as Bak. Herein, we describe the discovery of small-mol. inhibitors of the Mcl-1 oncoprotein based on a novel chemotype. Particularly, re-engineering of our 伪-helix mimetic JY-1-106 into 2,6-di-substituted nicotinates afforded inhibitors of comparable potencies but with significantly decreased mol. weights The most potent inhibitor 2-(benzyloxy)-6-(4-chloro-3,5-dimethylphenoxy)nicotinic acid (1 r: K_i=2.90 渭m) likely binds in the p2 pocket of Mcl-1 and engages R263 in a salt bridge through its carboxylic acid, as supported by 2D ¹H-¹⁵N HSQC NMR data. Significantly, inhibitors were easily accessed in just four steps, which will facilitate future optimization efforts. In the experiment, the researchers used many compounds, for example, Methyl 6-chloro-2-methoxynicotinate (cas: 65515-32-4Synthetic Route of C8H8ClNO3).

Methyl 6-chloro-2-methoxynicotinate (cas: 65515-32-4) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Alkyl chlorides are versatile building blocks in organic chemistry. While alkyl bromides and iodides are more reactive, alkyl chlorides tend to be less expensive and more readily available.Synthetic Route of C8H8ClNO3

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Novel Biphenyl Pyridines as Potent Small-Molecule Inhibitors Targeting the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction was written by Wang, Tianyu;Cai, Shi;Wang, Mingming;Zhang, Wanheng;Zhang, Kuojun;Chen, Dong;Li, Zheng;Jiang, Sheng. And the article was included in Journal of Medicinal Chemistry in 2021.Reference of 65515-32-4 This article mentions the following:

The design, synthesis and in-vitro and in-vivo evaluation of a series of novel biphenyl pyridines, I [R = Ph, 3-methoxyphenyl, 1,3-benzodioxol-5-yl, etc.; R¹ = H, (2-hydroxyethylamino)methyl; R² = methoxycarbonyl, (2-hydroxyethylamino)methyl, [[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl, etc.; R³ = H, MeO] as the inhibitors of PD-1/PD-L1 was reported. Compound I [R = Ph, R¹ = H, R² = (2-hydroxyethylamino)methyl, R³ = MeO] was found to inhibit the PD-1/PD-L1 interaction with an IC₅₀ value of 3.8 卤 0.3 nM and enhance the killing activity of tumor cells by immune cells. Compound I [R = Ph, R¹ = H, R² = (2-hydroxyethylamino)methyl, R³ = MeO] displayed great pharmacokinetics (oral bioavailability of 22%) and significant in-vivo antitumor activity in a CT26 mouse model. Flow cytometry and immunohistochem. data indicated that compound I [R = Ph, R¹ = H, R² = (2-hydroxyethylamino)methyl, R³ = MeO] activates the immune activity in tumors. These results suggest that compound I [R = Ph, R¹ = H, R² = (2-hydroxyethylamino)methyl, R³ = MeO] is a promising small-mol. inhibitor against the PD-1/PD-L1 axis and merits further development. In the experiment, the researchers used many compounds, for example, Methyl 6-chloro-2-methoxynicotinate (cas: 65515-32-4Reference of 65515-32-4).

Methyl 6-chloro-2-methoxynicotinate (cas: 65515-32-4) belongs to organic chlorides. Chlorination modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than water due to the higher atomic weight of chlorine versus hydrogen. Alkyl chlorides readily react with amines to give substituted amines. Alkyl chlorides are substituted by softer halides such as the iodide in the Finkelstein reaction.Reference of 65515-32-4

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics