Discovery of BMS-986202: A Clinical Tyk2 Inhibitor that Binds to Tyk2 JH2 was written by Liu, Chunjian;Lin, James;Langevine, Charles;Smith, Daniel;Li, Jianqing;Tokarski, John S.;Khan, Javed;Ruzanov, Max;Strnad, Joann;Zupa-Fernandez, Adriana;Cheng, Lihong;Gillooly, Kathleen M.;Shuster, David;Zhang, Yifan;Thankappan, Anil;McIntyre, Kim W.;Chaudhry, Charu;Elzinga, Paul A.;Chiney, Manoj;Chimalakonda, Anjaneya;Lombardo, Louis J.;Macor, John E.;Carter, Percy H.;Burke, James R.;Weinstein, David S.. And the article was included in Journal of Medicinal Chemistry in 2021.Electric Literature of C8H9ClN2O This article mentions the following:
A search for structurally diversified Tyk2 JH2 ligands from 6 (BMS-986165), a pyridazine carboxamide-derived Tyk2 JH2 ligand as a clin. Tyk2 inhibitor currently in late development for the treatment of psoriasis, began with a survey of six-membered heteroaryl groups in place of the N-Me triazolyl moiety in 6. The x-ray co-crystal structure of an early lead (12) revealed a potential new binding pocket. Exploration of the new pocket resulted in two front-runners for a clin. candidate. The potential hydrogen bonding interaction with Thr599 in the pocket was achieved with a tertiary amide moiety, confirmed by the x-ray co-crystal structure of 29. When the diversity search was extended to nicotinamides, a single fluorine atom addition was found to significantly enhance the permeability, which directly led to the discovery of 7 (BMS-986202) as a clin. Tyk2 inhibitor that binds to Tyk2 JH2. The preclin. studies of 7, including efficacy studies in mouse models of IL-23-driven acanthosis, anti-CD40-induced colitis, and spontaneous lupus, will also be presented. In the experiment, the researchers used many compounds, for example, 6-Chloro-N,N-dimethylnicotinamide (cas: 54864-83-4Electric Literature of C8H9ClN2O).
6-Chloro-N,N-dimethylnicotinamide (cas: 54864-83-4) belongs to amides. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, such as in the amino acids asparagine and glutamine. Amides are stable compounds. The lower-melting members (such as acetamide) can be readily purified by fractional distillation. Most amides are solids which have low solubilities in water.Electric Literature of C8H9ClN2O
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics