19690-23-4Relevant articles and documents
FragLites - Minimal, Halogenated Fragments Displaying Pharmacophore Doublets. An Efficient Approach to Druggability Assessment and Hit Generation
Wood, Daniel J.,Lopez-Fernandez, J. Daniel,Knight, Leanne E.,Al-Khawaldeh, Islam,Gai, Conghao,Lin, Shengying,Martin, Mathew P.,Miller, Duncan C.,Cano, Céline,Endicott, Jane A.,Hardcastle, Ian R.,Noble, Martin E. M.,Waring, Michael J.
, p. 3741 - 3752 (2019)
Identifying ligand binding sites on proteins is a critical step in target-based drug discovery. Current approaches to this require resource-intensive screening of large libraries of lead-like or fragment molecules. Here, we describe an efficient and effective experimental approach to mapping interaction sites using a set of halogenated compounds expressing paired hydrogen-bonding motifs, termed FragLites. The FragLites identify productive drug-like interactions, which are identified sensitively and unambiguously by X-ray crystallography, exploiting the anomalous scattering of the halogen substituent. This mapping of protein interaction surfaces provides an assessment of druggability and can identify efficient start points for the de novo design of hit molecules incorporating the interacting motifs. The approach is illustrated by mapping cyclin-dependent kinase 2, which successfully identifies orthosteric and allosteric sites. The hits were rapidly elaborated to develop efficient lead-like molecules. Hence, the approach provides a new method of identifying ligand sites, assessing tractability and discovering new leads.
Synthesis of some biologically active halogenopurines
Hu, Yu Lin,Liu, Xiang,Lu, Ming,Ge, Qiang,Liu, Xiao Bin
experimental part, p. 429 - 436 (2010/12/29)
A series of some biologically active halogenopurines were synthesized from commercially available guanine (1). The reaction of guanine with acetic anhydride yielded 2,9-diacetylguanine (2-1) by acetylation reaction. Further treatment of 2-1 with POCl3 by PEG-2000 phase transfer catalysis furnished the important compound 3a, then 2-amino-6-halogenopurines (3b-d) were obtained through chlorine-exchange halogenations between KX and 3a by TPPB phase transfer catalyst. Further, 2-halogenopurines (2-2a-d, 4-2a-d, 5a-d) were efficiently prepared from 2-amino-6-substituted purines (1, 3a, 4-1) via a diazotization catalyzed by their corresponding CuX, and some new compounds 2-2a, 2-2c, 2-2d, 4-2c, 4-2d, 5b, 5c and 5d have been discovered. The structures of synthesized compounds were mainly established on the basis of their elemental analysis, 1H NMR, as well as their mass spectral data. All the title compounds were screened for their antifungal activities, and some of the compounds showed promising activity.
Process for preparing guanine-containing antiviral agents and purinyl salts useful in such process
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, (2008/06/13)
A purine salt of the formula STR1 wherein Y1 is chloro, bromo, or iodo, and R1, R2, R3, and R4 are independently selected from alkyl and substituted alkyl is reacted with the compound of the formula to yield the purine of the formula STR2 wherein x is a leaving group, and Z1 is a protected form of the carbohydrate surrogate Z. Several routes are disclosed for converting this intermediate to the antiviral agent STR3
