Model structure–activity relationship studies of potential tropane 5HT1A, 5HT2A, and D2 receptor ligands

Abstract

The two-stages studies of structure–activity relationship for model ligands of 5HT1A, 5HT2A, and D2 receptors were performed. On the first stage, the pharmacophores of two potential ligands of known in vitro binding to 5HT1A, 5HT2A, D2 receptors and model pharmacophore of strongly interacting D2 receptor ligands were found and their parameters were related to affinity data. The analyzed parameters were hydrophobic, hydrophilic, aromatic, donor and acceptor of proton centers. The geometry of spatial distribution of these properties was also investigated in comparative analysis. The studied, model compounds were two 3β-acylamine derivatives of tropane. The second stage includes docking of studied compounds to D2 receptor model and the comparison of its quality with in vivo binding data. The obtained results are consistent with in vitro binding data and applied procedure accurate estimates the affinity of potential ligands to D2 receptors.

Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity

“…Here, we report the identification of several tropanes from various structural classes capable of significantly increasing neurite outgrowth while exhibiting greatly reduced activity at all MRs. Interestingly, these compounds appear to promote plasticity without directly activating the 5-HT2AR or 5-HT2CR. Tropane containing molecules are known to modulate several receptors that are implicated in various forms of plasticity including sigma-1 receptors, − dopamine receptors, − monoamine transporters, , adrenergic receptors, , opioid receptors, − and nicotinic acetylcholine receptors. , However, a common target shared by all psychoplastogenic tropanes is not obvious. Consequently, it is unclear if psychoplastogenic tropanes share a common target, or if their effects are the result of polypharmacological mechanisms.…”

A method for rapid screening of interactions of pharmacologically active compounds with albumin

“…The cefaclor, etodolac, sulindac, alpha-tris-(hydroxymethyl)-methylamine (tris) and bovine serum albumin (BSA) were purchased from Sigma-Aldrich Chemie (Steinheim, Germany), the 3b-and 3a-aminotropane derivatives (compounds [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] were synthesized at the Department of Drug Technology and Pharmaceutical Biotechnology at the Medical University of Warsaw. Ortho-phosphoric acid (H 3 PO 4 ) was purchased from POCH (Gliwice, Poland).…”

“…The compounds were obtained in a search for a new generation of antipsychotics following the principles of the multitarget strategy. The derivatives were designed for 5-HT 2A and D 2 receptors (the basic profile of pharmaceutical activity of atypical antipsychotics) and, additionally, for 5-HT 1A receptors [19][20][21][22][23][24][25]. With the aim of enhancing cognitive factors and memory, which might be improved by potential antipsychotics [26], the activity of the compounds was expanded to their affinity to 5-HT 1A receptors.…”

Synthesis and biological investigations of 3β-aminotropane arylamide derivatives with atypical antipsychotic profile

“…Our previous publications have described the synthesis and biological activity studies of new derivatives of 3β-aminotropane (Słowiński et al 2011, 2013; Stefanowicz et al 2016). Some of these derivatives demonstrate high activity at the D 2 , 5HT 1A , and 5-HT 2A receptors (Fig.…”