PTP1B inhibitors: Synthesis and evaluation of difluoro-methylenephosphonate bioisosteres on a sulfonamide scaffold

Chapter 6. Recent Advances in PTP1B Inhibitor Development for the Treatment of Type 2 Diabetes and Obesity

“…85 In probing F2PMP bioisosteres on a sulfonamide scaffold, a team from Affymax discovered compounds 33, 34, 35 as PTP1B inhibitors at low mM range, demonstrating the feasibility of this strategy in identifying non-phosphonate p-Tyr mimetics in a small molecule scaffold. 86 The selectivity and cell permeability data of these compounds were not reported. Recently, Zhang identified aryl diketoacids as novel p-Tyr surrogates and showed that neutral amide-linked aryl diketoacid dimers have excellent PTP inhibitory activity (compounds 36 and 37).…”

“…Cho identified several neutral PPP1B inhibitors via a structure-based virtual screening approach. 128 These compounds were structurally diverse and generally had IC 50 values less than 50 mM (compounds [85][86][87][88]. Docking studies showed that these inhibitors could be stabilized by multiple hydrogen bonds and van der Waals contacts in the active site.…”

Synthesis, Crystal Structure and Interaction with Bovine Serum Albumin (BSA) of Two α-Aminophosphonic Acids Derivatives

“…The formation of phosphorus-carbon bond has been received intense interest in recent years because the bond plays important role in a wide of biological properties and is able to function as a-aminocarboxylic acid surrogates reported that α-aminophosphonates could act as herbicides [5] or antibacterial [6], antiviral antitumor agents [8]. The potential of α aminophosphonates as enzyme inhibitors pharmacological agents has also been established [9][10][11][12][13][14][15]. Our previous studies have showed that some α-aminophosphonates could potently inhibit PTP1B and TCPTP with lower cytotoxicity [16].…”

4-Hydroxy-2-quinolones. 195*. Synthesis of novel, potential analgesics based on 4-(hetarylmethyl)amino-2-oxo-1,2-dihydro-quinoline-3-carboxylic acids

“…The concept of bioisosteric replacement had been proposed even at the beginning of the last century [2] and now remains one of the most powerful means of creating efficient and safe medicinal agents [3][4][5][6][7][8][9][10][11][12]. Its use allows not only the optimization of already known biologically active materials but also identifies novel structures with similar or related properties as well as increasing the patent protection of a current medicine.…”