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Carbonic anhydrase inhibitors. Preparation of potent sulfonamides inhibitors incorporating bile acid tails.

Abstract：

:Reaction of TBDMS-protected bile acids (cholic, chenodeoxycholic, deoxycholic, lithocholic, ursodeoxycholic acids) or dehydrocholic acid with aromatic/heterocyclic sulfonamides possessing free amino/hydroxy moieties, in the presence of carbodiimides, afforded after deprotection of the OTBDMS ethers, a series of sulfonamides incorporating bile acid moieties in their molecules. Many such derivatives showed strong inhibitory properties against three isozymes of carbonic anhydrase (CA, EC 4.2.1.1), that is CA I, II and IV, zinc enzymes playing critical roles in many pathologies, and which represent interesting targets for developing diverse pharmacological agents. Some of the most active derivatives, incorporating 1,3,4-thiadiazole-2-sulfonamide or benzothiazole-2-sulfonamide functionalities in their molecules, showed low nanomolar affinity for CA II and CAIV. Furthermore, the bioavailability of these derivatives in rabbits is comparable to that of acetazolamide, being in the range of 85-90%, showing them as promising candidates for systemically acting CA inhibitors.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Scozzafava A,Supuran CT

doi

10.1016/s0960-894x(02)00252-4

subject

Has Abstract

pub_date

2002-06-17 00:00:00

pages

1551-7

issue

12

eissn

0960-894X

issn

1464-3405

pii

S0960894X02002524

journal_volume

12

pub_type

杂志文章

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