Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors.

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Gitto R, Damiano FM, De Luca L, Ferro S, Vullo D, Supuran CT, Chimirri A

Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors.

Bioorg Med Chem. 2011 Dec 1;19(23):7003-7. doi: 10.1016/j.bmc.2011.10.015. Epub 2011 Oct 12.

PubMed ID

22041171 [ View in PubMed

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Abstract

In a previous paper we identified several 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-sulfonamides that displayed inhibitory effects toward selected carbonic anhydrase isozymes at micromolar concentration. In order to deepen the structure-activity relationships (SARs) and identify novel compounds with improved activity, we synthesized a series of monomethoxy analogues of the previously investigated dimethoxy derivatives. The evaluation of biological profile has been focused on in vitro effects against several CA isoforms. The new monomethoxy derivatives showed higher hCA inhibitory effects against several isoforms compared to the dimethoxy analogues. Particularly, some of these compounds (e.g., 1b and 1h) showed low nanomolar K(I) values and excellent selectivity for hCA IX and hCA XIV versus hCA I and II inhibition.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Zonisamide	Carbonic anhydrase 1	Ki (nM)	56	N/A	N/A	Details
Zonisamide	Carbonic anhydrase 14	Ki (nM)	5250	N/A	N/A	Details
Zonisamide	Carbonic anhydrase 2	Ki (nM)	35	N/A	N/A	Details
Zonisamide	Carbonic anhydrase 9	Ki (nM)	5.1	N/A	N/A	Details