Discovery of novel and potent heterocyclic carboxylic acid derivatives as protein tyrosine phosphatase 1B inhibitors

Substituted oxadiazoles: a patent review (2010 – 2012)

“…Kimura et al synthesized pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres, based on modification of previously reported potent BACE1 inhibitor KMI-420 [71] (IC 50 = 8.2 nM) (41). Although KMI-420 exhibited potent inhibitory activity, acidic moieties (carboxylic groups) often possess low membrane permeability across the blood--brain barrier.…”

“…The SAR of this class of compounds showed that the presence of an isoxazole, thiazole ring and 1,2-diphenyl ethanone group is sufficient to afford potent PTP1B inhibitors and even more potent inhibitors obtained by incorporation of an oxadiazole (compound 18). Compound 18 displayed good in vitro potency (K i = 0.3 µM), selectivity, acceptable absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetic properties in mice and showed 36% oral bioavailability [41].…”

Design, synthesis, and pharmacology of some oxadiazole and hydroxypyrazoline hybrids bearing thiazoyl scaffold: antiproliferative activity, molecular docking and DNA binding studies

“…On the other hand, there are a bunch of reports on 1,3,4-oxadiazoles exhibiting various pharmacological activities, such as anti-diabetic [20], antihypertension [21], analgesic [22], antiviral [23], anticonvulsant [24], antifungal [25] antibacterial [26], anticancer [27], anti-glycation [28], anti-inflammatory [29], antimicrobial [30], and ulcerogenic [31]. Compounds containing oxadiazole units such as Nesapidil, Furamizole, and Zibotentan [32] (Fig.…”

DBU‐Mediated [3+2] Cycloaddition Reactions of Donor–Acceptor Cyclopropanes with Nitromethane: Efficient Strategy for the Construction of Isoxazole Skeletons

“…The 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU) mediated reactions proceeded smoothly under basic conditions to afford isoxazole-5-carboxylate derivatives. It is well known that the isoxazole unit is a key structural motif in a large number of natural products and pharmaceutically active compounds, and, in particular, functionalized isoxazoles, such as isoxazole-5-carboxylate derivatives, have been synthesized and used as potential HIV-1 protease inhibitors, [19] anti-inflammatory, [20] antiviral, [21] antibiotic, [22] antidepressant, [23] and antifungal agents, [24] DGAT1 inhibitors as anti-obesity agents, [25] potent, selective, and metabolically stable PTP1B inhibitors, [26] and show antitubulin [27] activity as antitumor agents. In addition, the isoxazole ring system is a useful synthetic building block.…”