Structure–Activity relationships of non-imidazole H3 Receptor ligands. Part 2: binding preference for d-Amino acids motifs

Identification of novel H 3 receptor (H 3 R) antagonists with cognition enhancing properties in rats

“…A-304121 (2-Amino-1-{4-[3-(4-cyclopropanecarbonyl-phenoxy)-propyl]-piperazin-1-yl}-propan-1-one) and A-317920 (Furan-2-carboxylic acid (2-{4-[3-(4-cyclopropanecarbonyl-phenoxy)-propyl]-piperazin-1-yl}-1-methyl-2-oxo-ethyl)-amide), were synthesized at Abbott [5] and evaluated in a repeated acquisition, avoidance model using methods similar to those previously described [1]. Briefly, male spontaneously hypertensive rat (SHR) pups (postnatal day 20 -24) were trained to avoid a mild footshock (0.1 mA, 1 s duration), delivered when the pup transferred from a brightly lit to a darkened compartment.…”

D-alanine piperazine-amides: novel non-imidazole antagonists of the histamine H 3 receptor

“…A-304121 (1) is a new member of a small group of non-imidazole H 3 receptor ligands [3]. This compound was shown to be highly potent at the rat H 3 receptor.…”

“…A-304121 (compound 1, Table 1) was prepared as described by Faghih [3]. N-acyl, sulfonamides, sulfonylureas and ureas were prepared using standard acylation chemistry to give compounds 2 -10.…”

Molecular modeling of histamine H3 receptor and QSAR studies on arylbenzofuran derived H3 antagonists

“…Blockade of the histamine H3 autoreceptors by antagonists interrupts a negative feedback mechanism and leads to increased levels of histamine and other neurotransmitters. The central effects of the H3 receptor antagonists suggest a potential therapeutic role for the treatment of several diseases and neurological disorders such as epilepsy, obesity, arousal, attention-deficit hyperactivity disorder (ADHD], schizophrenia, Alzheimer's and Parkinson's diseases [5,[9][10][11]. Recent evidence supports the idea that the combination of an H1 antagonist with an H3 antagonist acts as a nasal decongestant [12].…”