Oligohalogenated Arylaldehydes for Drug Discovery Projects

Mono-, di-, tri-, tetra-, and penta-halogenated benzene rings are substructures of numerous approved and experimental drugs,¹ agrochemicals² and natural products.³ The halogenated compounds generally have higher biological activity and membrane permeability compared to their non-halogenated congeners.⁴

Selected examples of dihalogenated benzene ring substructures, found amongst approved, experimental, and investigational drugs, are presented in Figure 1.

Figure 1. Selected examples of dihalogenated benzene substructures found amongst approved, experimental (exp.), and investigational (invest.) drugs. Substituents R1 - R4 stand for any atom or group. The data on substructures are as of April 2019.

In view of a very high involvement of oligohalogenated aromatic subunits into structural design of biologically active compounds, it is of importance for those engaged in drug discovery projects to get access to aromatic building blocks with variable halogenation patterns. 

In this context Life Chemicals Inc. is offering structurally diverse oligohalogenated benzaldehyde derivatives as well as their heterocyclic analogues that include pyridine, quinoline and thiophene substructures. The rich chemistry of the aldehyde group combined with the ease of the nucleophilic displacement of a halogen in these compounds are completely suitable for preparation of fragment and screening libraries.

Scheme 1 provides an example in which 2-fluorobenzaldehydes undergo cyclocondensation with different amidines to yield biologically potent quinazolines.⁵

Scheme 1. Example of qunazoline synthesis through condensation of 2-florobenzaldehydes with amidines. Adopted from ref. 5a.

There are in total 123 analogues available from our stock, see the representative set below. To explore the full data set, please send your request to orders@lifechemicals.com.

References

1. According to drugbank.ca (accessed in April 2019) there are over 200 approved and investigational drugs that contain benzene ring substructures bearing two or more halogen atoms.
2. Herrera-Rodriguez, L. N.; Khan, F.; Robins, K. T.; Meyer, H.-P. Chim. Oggi 2011, 29, 31–33.
3. Cantillo, D.; Kappe, C. O. React. Chem. Eng. 2017, 2, 7-19.
4. Blasiak, L. C.; Drennan, C. L. Acc. Chem. Res. 2009, 42, 147–155.
5. (a) Kotzuki, H.; Sakai, H.; Morimoto, H.; Suenaga, H. Synlett 1999, 1993-95. (b) Li, C.; Shan, Y.; Sun, Y.; Si, R.; Liang, L.; Pan, X. Eur. J. Med. Chem. 2017, 141, 506-518.