New and unusual scaffolds in medicinal chemistry

Abstract

Contemporary medicinal chemistry faces diverse challenges from several directions, including the need for both potency and specificity of any therapeutic agent; the increasingly demanding requirements of low toxicity shown across all patients treated; and the need for novelty in intellectual property, given the extensive use of benzenoid and heteroaromatic ring systems in numerous patents. Increasingly, such challenges are being met by a shift to new and/or unusual ring systems (scaffolds) that lie outside the field of (hetero)aromatic systems. This critical review surveys a necessarily limited selection of currently atypical scaffolds, chiefly drawn from the literature of the last three years, that have found application in medicinal chemistry, some being present in agents with therapeutic potential while others are found in agents already in clinical use (163 references).

Synthesis and evaluation of sulfonamide-bearing thiazole as carbonic anhydrase isoforms hCA I and hCA II

“…Heterocyclic moieties, such as indoles, thiazolidine-4-ones, pyrazoles, piperazines, pyridines, etc., always have considerable attention due to their pharmacological activities 1,2 . Heterocycles bearing one or more nitrogen and sulfur atoms have received more attention recently.…”

Access to novel imidazo[1,5-a]pyrazine scaffolds by the combined use of a three-component reaction and a base-assisted intramolecular cyclization

“…Benzyl N- [2-(4-chlorophenyl)-8-methyl-6-methylene-1-oxo-3-thioxo-1,2,3,5,7-hexahydroimidazo[1,5-a] 5.21 (s,2H),7H),7.56 (d,J = 8.4 Hz,2H), 10.59 (s, 1H); 13 C NMR (100 MHz,18.3,44.3,67.0,95.1,105.6,127.9,128.2,128.5,128.7,130.5,132.6,133.0,135.7,136.0,141.2,155.1,159.7,169.2;MS (EI) m/z (%) 470 [M + + 2 (7)], 468 (M + , 20), 333 (9), 319 (14), 298 (13), 169 (12), 149 (56), 121 (100) , 4.51; N, 11.95; found C, 58.78; H, 4.63; N, 11.84.…”

The solid state structure of pyridinium hydrogen squarate

“…All can participate in hydrogen-bonding interactions: whereas squarate dianion can only act as a strong hydrogen bond acceptor, the parent acid and its mononeutralized form, HSq -ion, are both potent donors and acceptors. Recent research on the acid and its anions has been focused on their applications as active pharmaceutical ingredients [4][5][6], or fluorescent biomarkers with large second-and third-order nonlinear optical responses [7,8]. Their application in crystal engineering has also been reported [9,10] [11].…”