Discovery and structure-based design of 4,6-diaminonicotinamides as potent and selective IRAK4 inhibitors.

Bhide, Rajeev S; Keon, Alec; Weigelt, Carolyn; Sack, John S; Schmidt, Robert J; Lin, Shuqun; Xiao, Hai-Yun; Spergel, Steven H; Kempson, James; Pitts, William J; Carman, Julie; Poss, Michael A

Bhide, Rajeev S; Keon, Alec; Weigelt, Carolyn; Sack, John S; Schmidt, Robert J; Lin, Shuqun; Xiao, Hai-Yun; Spergel, Steven H; Kempson, James; Pitts, William J; Carman, Julie; Poss, Michael A.

Affiliation

Bhide RS; Discovery Chemistry, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States. Electronic address: bhider09@gmail.com.
Keon A; Discovery Chemistry, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Weigelt C; Molecular Structure and Design, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Sack JS; Molecular Structure and Design, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Schmidt RJ; Discovery Chemistry, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Lin S; Discovery Chemistry, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Xiao HY; Discovery Chemistry, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Spergel SH; Discovery Chemistry, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Kempson J; Discovery Chemistry, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Pitts WJ; Discovery Chemistry, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Carman J; Immunoscience Biology, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
Poss MA; Discovery Chemistry, Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.

Bioorg Med Chem Lett ; 27(21): 4908-4913, 2017 11 01.

Article in En | MEDLINE | ID: mdl-28947151

Subject(s)

Drug Design; Interleukin-1 Receptor-Associated Kinases/antagonists & inhibitors; Niacinamide/chemistry; Protein Kinase Inhibitors/chemistry; Binding Sites; Crystallography, X-Ray; Drug Evaluation, Preclinical; Humans; Inhibitory Concentration 50; Interleukin-1 Receptor-Associated Kinases/metabolism; Janus Kinase 3/chemistry; Janus Kinase 3/metabolism; Molecular Conformation; Molecular Dynamics Simulation; Niacinamide/metabolism; Protein Kinase Inhibitors/metabolism; Protein Structure, Tertiary; Structure-Activity Relationship

Key words

4,6-Diaminonicotinamide; Autoimmune disease; IRAK4; Rheumatoid arthritis

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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Design / Niacinamide / Protein Kinase Inhibitors / Interleukin-1 Receptor-Associated Kinases Limits: Humans Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2017 Document type: Article

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