Asymmetric Synthesis of CIDD-0072424 via an Enantioselective Nitro-Mannich Reaction: A Central Nervous System Penetrant, Selective Small Molecule Inhibitor of Protein Kinase C Epsilon.

Autor:	De Kraker H; Center for Innovative Drug Discovery, Department of Chemistry, University of Texas San Antonio, San Antonio, Texas 78254, United States., Wang HL; Center for Innovative Drug Discovery, Department of Chemistry, University of Texas San Antonio, San Antonio, Texas 78254, United States., Arman HD; Center for Innovative Drug Discovery, Department of Chemistry, University of Texas San Antonio, San Antonio, Texas 78254, United States., Renteria RN; Center for Innovative Drug Discovery, Department of Chemistry, University of Texas San Antonio, San Antonio, Texas 78254, United States., Fleischer CN; College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States., Messing RO; College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States., McHardy SF; Center for Innovative Drug Discovery, Department of Chemistry, University of Texas San Antonio, San Antonio, Texas 78254, United States.
Jazyk:	angličtina
Zdroj:	The Journal of organic chemistry [J Org Chem] 2024 Apr 05; Vol. 89 (7), pp. 5134-5141. Date of Electronic Publication: 2024 Mar 15.
DOI:	10.1021/acs.joc.3c02917
Abstrakt:	CIDD-0072424 is a novel small molecule developed in silico with remarkable activity for the inhibition of protein kinase C (PKC)-epsilon to treat alcohol use disorder. We developed a concise synthesis of ( S )- 2 that is highly enantioselective, scalable, and amenable for 3-point structure-activity relationship (SAR) studies for compound optimization. The highly enantioselective nitro-Mannich reaction was achieved through a dual-reagent catalysis system. The overall utility and the efficiency of the enantioselective route provided a scalable synthesis of both PKCε inhibitors 1 and 2 .
Databáze:	MEDLINE
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