Discovery of SARxxxx92, a pan-PIM kinase Inhibitor, efficacious in a KG1 tumor model,Bioorganic & Medicinal Chemistry Letters

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Discovery of SARxxxx92, a pan-PIM kinase Inhibitor, efficacious in a KG1 tumor model
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2020-10-20 , DOI: 10.1016/j.bmcl.2020.127625
Claude Barberis ₁ , Paul Erdman ₂ , Mark Czekaj ₁ , Luke Fire ₃ , James Pribish ₁ , Elina Tserlin ₄ , Sachin Maniar ₁ , Joseph D Batchelor ₁ , Jinyu Liu ₁ , Vinod F Patel ₅ , Andrew Hebert ₆ , Mikhail Levit ₆ , Anlai Wang ₇ , Frank Sun ₈ , Shih-Min A Huang ₉

Affiliation

IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States.
IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States; Present address: AbbVie, 100 Abbott Park Road, Abbott Park, IL 60064-3500, United States.
IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States; Present address: Rakuten Medical, 11080 Roselle St, San Diego, CA 92121, United States.
Present address: Qiagen, 561 Virginia Road, Concord, MA 01742, United States.
Present address: TME Therapeutics, 3 Mossy Lane, Acton, MA 01720, United States.
Oncology Biochemistry, Sanofi, 270 Albany Street, Cambridge MA 02139, United States.
Oncology Biology, Sanofi, 270 Albany Street, Cambridge MA 02139, United States.
Oncology Pharmacology, Sanofi, 640 Memorial Drive, Cambridge MA 02139, United States.
Oncology Biology, Sanofi, 270 Albany Street, Cambridge MA 02139, United States; Present address: Bristol-Myers Squibb, 3551 Lawrenceville Princeton, Lawrence Township, NJ 08648, United States.

N-substituted azaindoles were discovered as potent pan-PIM inhibitors. Lead optimization, guided by structure and focused on physico-chemical properties allowed us to solve inherent hERG and permeability liabilities, and provided compound 27, which subsequently impacted KG-1 tumor growth in a mouse model.

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