title: A Highly Efficient Diversification of 2-Amino/Amido-1,3,4-oxadiazole and 1,3,4-Thiadiazole Derivatives via Reagent-Based Cyclization of Thiosemicarbazide Intermediate on Solid-Phase.
abstract: A 2-amino/amido-1,3,4-oxadiazole and 1,3,4-thiadiazole library has been constructed on solid-phase organic synthesis. The key step on this solid-phase synthesis involves the preparation of polymer-bound 2-amino-1,3,4-oxadiazole and 1,3,4-thiadiazole core skeleton resin by cyclization of thiosemicarbazide with EDC·HCl and p-TsCl, respectively. The resulting core skeleton undergoes functionalization reaction with various electrophiles such as alkyl halides, and acid chlorides to generate N-alkylamino and N-acylamino-1,3,4-oxadiazole, and 1,3,4-thiadiazole resin, respectively. Finally, the 2-amino and 2-amido-1,3,4-oxadiazole and 1,3,4-thiadiazole library was then generated in good yields and high purities by cleavage of the respective resin under trifluoroacetic acid(TFA) in dichloromethane(DCM). The constructed library shows reasonable, oral bioavailability drug properties as determine by using the Lipinski's Rule and similar parameters.
authors.affiliation: Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
authors.forename: Seung-Ju
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Choe
authors.affiliation: Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
authors.forename: Aizhan
authors.initials: A
authors.lastname: Abdildinova
authors.affiliation: Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
authors.forename: Young-Dae
authors.initials: YD
authors.lastname: Gong
mesh_terms: D003500:Cyclization; D007202:Indicators and Reagents / Q000737:chemistry; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry*; D012663:Semicarbazides / Q000138:chemical synthesis* / Q000737:chemistry; D013830:Thiadiazoles / Q000737:chemistry*
chemical_list: D007202:Indicators and Reagents; D010069:Oxadiazoles; D012663:Semicarbazides; D013830:Thiadiazoles; C583463:1,3,4-oxadiazole; C005151:thiosemicarbazide
keywords: 1,3,4-oxadiazole; 1,3,4-thiadiazole; BOMBA; solid-phase; thiosemicarbazide