Acidic elements in histamine H(3) receptor antagonists.

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Sander K, von Coburg Y, Camelin JC, Ligneau X, Rau O, Schubert-Zsilavecz M, Schwartz JC, Stark H

Acidic elements in histamine H(3) receptor antagonists.

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1581-4. doi: 10.1016/j.bmcl.2010.01.089. Epub 2010 Jan 21.

PubMed ID

20138762 [ View in PubMed

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Abstract

Antagonists of the human histamine H(3) receptor (hH(3)R) often contain a second basic moiety, which is well known to boost affinity on this histamine receptor subtype. Here, we prepared compounds with acidic moieties of different pK(a) values to figure out that the hH(3)R tolerates these functionalities when added to a common pharmacophore blueprint. Depending on the acidic, electronic and steric features the designed ligands showed hH(3)R affinities in the nanomolar concentration range. Additionally, selected ligands were tested but failed as dual acting hH(3)R/hPPAR (human peroxisome proliferator-activated receptor) ligands.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rosiglitazone	Peroxisome proliferator-activated receptor alpha	EC 50 (nM)	>10000	N/A	N/A	Details
Rosiglitazone	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	30	N/A	N/A	Details
Rosiglitazone	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	100	N/A	N/A	Details