853759-00-9Relevant academic research and scientific papers
Synthetic methodology for the preparation of N-hydroxysulfamides
Devanathan, Krishnaswamy,Bell, Jennifer A.,Wilkins, Patricia C.,Jacobs, Hollie K.,Gopalan, Aravamudan S.
, p. 8029 - 8033 (2007)
A convenient synthesis of a variety of substituted N-hydroxysulfamides from chlorosulfonyl isocyanate is reported. Alkyl groups can be introduced selectively on the N-Boc nitrogen of key intermediates 1a or 1b using the Mitsunobu reaction with alcohols. S
Carbonic anhydrase inhibitors: Synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, IX, and XII with N-hydroxysulfamides - A new zinc-binding function in the design of inhibitors
Winum, Jean-Yves,Innocenti, Alessio,Nasr, Jihane,Montero, Jean-Louis,Scozzafava, Andrea,Vullo, Daniela,Supuran, Claudiu T.
, p. 2353 - 2358 (2005)
A small library of N-hydroxysulfamides was synthesized by an original approach in order to investigate whether this zinc-binding function is efficient for the design of inhibitors targeting the cytosolic (hCA I and II) and transmembrane, tumor-associated (hCA IX and XII) isozymes of carbonic anhydrase (CA, EC 4.2.1.1). The parent derivative, N-hydroxysulfamide was a more potent inhibitor as compared to sulfamide or sulfamic acid against all isozymes, with inhibition constants in the range of 473 nM-4.05 μM. Its substituted n-decyl-, n-dodecyl-, benzyl-, and biphenylmethyl-derivatives were less inhibitory against hCA I (KIs in the range of 5.8-8.2 μM) but more inhibitory against hCA II (KIs in the range of 50.5-473 nM). The same situation was true for the tumor-associated isozymes, with KIs in the range of 353-790 nM against hCA IX and 372-874 nM against hCA XII. Some sulfamides/sulfamates possessing similar substitution patterns have also been investigated for the inhibition of these isozymes, being shown that in some particular cases sulfamides are more efficient inhibitors as compared to the corresponding sulfamates. Potent CA inhibitors targeting the cytosolic or tumor-associated CA isozymes can thus be designed from various classes of sulfonamides, sulfamides, or sulfamates and their derivatives, considering the extensive interactions in which the inhibitor and the enzyme active site are engaged, based on recent X-ray crystallographic data.
