Parallel Synthesis of bis-heterocyclic isoxazolylmethyl- and isoxazolinylmethylpyrazoles.
The solution-phase parallel synthesis of a 136-member library of isoxazol(in)e-CH(2)-pyrazoles is described. X-ray crystallographic structure determination verified the regioselectivities of the N-alkylation and nitrile oxide 1,3-dipolar cycloaddition steps. The construction of these pharmaceutically relevant heterocycles on solid support under microwave irradiation is also demonstrated. The resulting library of drug-like compounds has been added to the National Institutes of Health repository (approximately 10 mg of each with >or=90% purity) for pilot-scale biomedical studies with bioassay data available at the National Center for Biotechnology Information PubChem database. A subset of these compounds has been broadly screened by Dow AgroSciences for herbicidal, fungicidal, and insecticidal activity.
Meng
Liping
L
Department of Chemistry, University of California, Davis, Davis, California 95616, USA.
Lorsbach
Beth A
BA
Sparks
Thomas C
TC
Fettinger
James C
JC
Kurth
Mark J
MJ
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D006571:Heterocyclic Compounds; D010069:Oxadiazoles; D004364:Pharmaceutical Preparations; D011720:Pyrazoles