Scaffolding-Induced Property Modulation of Chemical Space

Abstract

Physicochemical property switching of chemical space is of great importance for optimization of compounds, for example, for biological activity. Cyclization is a key method to control 3D and other properties. A two-step approach, which involves a multicomponent reaction followed by cyclization, is reported to achieve the transition from basic moieties to charge neutral cyclic derivatives. A series of multisubstituted oxazolidinones, oxazinanones, and oxazepanones as well as their thio and sulfur derivatives are synthesized from readily available building blocks with mild conditions and high yields. Like a few other methods, MCR and cyclization allow for the collective transformation of a large chemical space into a related one with different properties.

In Silico Design and Selection of New Tetrahydroisoquinoline-Based CD44 Antagonist Candidates

“…The DrugBank Database drugs frequently adopt rod-and disc-shapes [37] and comply with Lipinski's Ro5 [33,38]. The compounds within our CCC-generated libraries predominantly displayed these shapes, due to the high predominance of non-cyclic molecules [37,39], and have drug-like physicochemical characteristics. Molecules with the THQ substructure have been identified as nicotinic [40] or muscarinic [41] receptor antagonists, in addition to inhibitors of the angiotensin-converting enzyme [42].…”

Synthesis of Fused Imidazoles and Pyrimidinones from 2‐Aminoazines

“…The reaction is compatible with a wide range of 2-aminoazines, aldehydes, and isonitriles. Numerous reaction conditions have been investigated, including a diversity of catalysts, solvent or solvent-free conditions, microwave irradiation, and conven- (compound 12), [17] scandium tris(trifluoromethanesulfonate) (Sc(OTf) 3 ) (compounds 16 and 19), [18] ytterbium triflate (Yb(OTf) 3 ), [19] calcium triflate (Ca(OTf) 2 ) (compound 14), [20] perchloric acid (HClO 4 ) (compound 20), [21] acetic acid (compounds 11, 13 and 21), [22] hydrogen chloride (compounds 17 and 22), [23,24] trifluoracetic acid (TFA), (Compound 18), [25] and sodium dodecyl sulphate (SDS) [26] have been used to promote the GBB reaction with high product yield. Biocatalysts, such as lipase enzymes, have also been used in the GBB reaction.…”

“…Biocatalysts, such as lipase enzymes, have also been used in the GBB reaction. [27] In addition to standard heating (compound 15), [28] advanced techniques that include MW irradiation (compounds 14, 17 and 22), [20,23,24] solid phase synthesis [22] and Brønsted acidic ionic liquids [29] have also been applied.…”

Discovery of Novel Bicyclic Imidazolopyridine-Containing Human Urate Transporter 1 Inhibitors as Hypouricemic Drug Candidates with Improved Efficacy and Favorable Druggability

“…Then, nucleophilic substitution and hydrolysis of 4b or 4c provided 33–38 . The preparation method of 39–44 is similar to that of 33–38 , except that the starting material is 4-chloro-3-nitropyridine . The purity of the representative final compounds was checked by ultrahigh-performance liquid chromatography (UHPLC), and all was ≥95%.…”

“…The synthetic route to 33−44 is outlined in Scheme 3. The starting material 4-cyclopropylnaphthalen-1-amine was treated with 2-nitropyridin-3-yl trifluoromethanesulfonate (1b) or 4- 46 The purity of the representative final compounds was checked by ultrahigh-performance liquid chromatography (UHPLC), and all was ≥95%.…”