title: Regioselective construction and screening of 1,3-disubstituted tetrahydroindazolones in enantiomerically pure pairs.
abstract: In this paper, we describe a regioselective synthetic pathway for enantiopure 1,3-disubstituted tetrahydroindazolone derivatives via the condensation of 2-acylcyclohexane-1,3-dione with various alkyl- and arylhydrazines using the steric effects of a Boc-protected pyrrolidine ring. This synthetic method has a broad scope for substrate generality for various hydrazines with excellent regioselectivity. To maximize the molecular diversity, further diversifications of 1,3-disubstituted tetrahydroindazolones were pursued by systematic N-modification of the secondary amine of the pyrrolidine ring using solution-phase parallel synthesis with polymer-supported reagents. A library containing a total of 272 drug-like tetrahydroindazolones, including 85 enantiomeric pairs, was constructed; the average purity, without further purification, was 95%.
authors: Department of Chemistry, Seoul National University, Korea.
authors: Heebum
authors: H
authors: Song
authors: Hanjae
authors: H
authors: Lee
authors: Jonghoon
authors: J
authors: Kim
authors: Seung Bum
authors: SB
authors: Park
mesh_terms: D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D007191:Indazoles; D054852:Small Molecule Libraries