22946-12-9Relevant academic research and scientific papers
Bioisosteric replacement and related analogs in the design, synthesis and evaluation of ligands for muscarinic acetylcholine receptors
Bhandare, Richie R.,Canney, Daniel J.
, p. 361 - 375 (2014/05/20)
Previous structure-activity relationship studies involving a series of lactone-based muscarinic ligands identified a lead compound containing a diphenylmethylpiperazine moiety (4; IC50 = 340 nM). The purpose of the present work is to investigate 1,3-benzodioxoles, 4,4-diethyl substituted tetrahydrofurans, 5-substituted oxazolidinones and chromones as bioisosteric replacements for the lactone ring in a novel series of muscarinic ligands. The approach provided compounds with improved % inhibition values and identified a non-selective muscarinic ligand with an IC50 value of 280 nM. The structure-activity relationship for this new series will be discussed. Selected compounds were evaluated in preliminary assays for subtype selectivity and were found to be non-selective.
OXIME COMPOUNDS AND THE USE THEREOF
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Page/Page column 364-365, (2008/06/13)
The invention relates to oxime compounds of Formula (I) and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein X is hydrogen, optionally substituted aryl, optionally substituted heteroaryl or the like; Y is CO, SO2, CRsu
Comparison of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II by using topiramate as a structural platform
Maryanoff, Bruce E.,McComsey, David F.,Costanzo, Michael J.,Hochman, Coralie,Smith-Swintosky, Virginia,Shank, Richard P.
, p. 1941 - 1947 (2007/10/03)
This paper examines the relative effectiveness of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II (CA-II). Topiramate (1) and its sulfamide analogue 4, and 4,5-cyclic sulfate 6 and its sulfamide analogue 5, were compared for inhibition of human CA-II. A colorimetric assay, based on the pH shift that accompanies hydration of carbon dioxide, and an esterase assay were used. For these bioisosteric pairs, 1/4 and 6/5, the sulfamate compound was markedly more potent than its sulfamide counterpart. A similar, large difference in potency was also observed for the sulfamate/sulfamide pairs 14/15 and 16/17. These results indicate that the sulfamide moiety is not particularly suitable for obtaining potent carbonic anhydrase inhibition. A discussion of this structure-activity relationship with respect to the interactions of 1 and 6 with CA-II from published X-ray data is presented. A metabolic acidosis study was performed in rats with 1, 4, 6, and 2, and the results are discussed with respect to the degree of inhibition of CA-II in vivo.
Discovery of a new class of potent, selective, and orally active prostaglandin D2 receptor antagonists
Torisu, Kazuhiko,Kobayashi, Kaoru,Iwahashi, Maki,Nakai, Yoshihiko,Onoda, Takahiro,Nagase, Toshihiko,Sugimoto, Isamu,Okada, Yutaka,Matsumoto, Ryoji,Nanbu, Fumio,Ohuchida, Shuichi,Nakai, Hisao,Toda, Masaaki
, p. 5361 - 5378 (2007/10/03)
N-(p-Alkoxy)benzoyl-2-methylindole-4-acetic acids 2r and 2s were identified as a new class of orally active prostaglandin D2 (PGD2) receptor antagonists. The process of discovering a series of N-(p-alkoxy)benzoyl-2-methylindole-4-ace
