In 2019,European Journal of Medicinal Chemistry included an article by Hogendorf, Adam S.; Hogendorf, Agata; Kurczab, Rafal; Kalinowska-Tluscik, Justyna; Popik, Piotr; Nikiforuk, Agnieszka; Krawczyk, Martyna; Satala, Grzegorz; Lenda, Tomasz; Knutelska, Joanna; Bugno, Ryszard; Staron, Jakub; Pietrus, Wojciech; Matloka, Mikolaj; Dubiel, Krzysztof; Moszczynski-Petkowski, Rafal; Pieczykolan, Jerzy; Wieczorek, Maciej; Pilarski, Boguslaw; Zajdel, Pawel; Bojarski, Andrzej J.. Recommanded Product: 1H-Imidazol-2-amine. The article was titled 《2-Aminoimidazole-based antagonists of the 5-HT6 receptor – A new concept in aminergic GPCR ligand design》. The information in the text is summarized as follows:
A new strategy in the design of aminergic GPCR ligands is proposed – the use of aromatic, heterocyclic basic moieties in place of the evergreen piperazine or alicyclic and aliphatic amines. This hypothesis has been tested using a benchmark series of 5-HT6R antagonists obtained by coupling variously substituted 2-aminoimidazole moieties to the well established 1-benzenesulfonyl-1H-indoles, which served as the ligands cores. The crystallog. studies revealed that upon protonation, the 2-aminoimidazole fragment triggers a resonance driven conformational change leading to a form of higher affinity. This mol. switch may be responsible for the observed differences in 5-HT6R activity of the studied chemotypes with different amine-like fragments. Considering the multiple functionalization sites of the embedded guanidine fragment, diverse libraries were constructed, and the relationships between the structure and activity, metabolic stability, and solubility were established. Compounds from the N-(1H-imidazol-2-yl)acylamide chemotype (10a-z) exhibited high affinity for 5-HT6R and very high selectivity over 5-HT1A, 5-HT2A, 5-HT7 and D2 receptors (negligible binding), which was attributed to their very weak basicity. The lead compound in the series 4-methyl-5-[1-(naphthalene-1-sulfonyl)-1H-indol-3-yl]-1H-imidazol-2-amine (9i) was shown to reverse the cognitive impairment caused by the administration of scopolamine in rats indicating procognitive potential. In the experiment, the researchers used 1H-Imidazol-2-amine(cas: 7720-39-0Recommanded Product: 1H-Imidazol-2-amine)
1H-Imidazol-2-amine(cas: 7720-39-0) belongs to anime. Primary amines having a tertiary alkyl group (R3CNH2) are difficult to prepare with most methods but are made industrially by the Ritter reaction. In this method a tertiary alcohol reacts with hydrogen cyanide (HCN) in the presence of a concentrated strong acid; a formamide, RNH―CHO, is formed first, which then undergoes hydrolysis.Recommanded Product: 1H-Imidazol-2-amine
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem