Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors

Biphenyl Sulfonylamino Methyl Bisphosphonic Acids as Inhibitors of Matrix Metalloproteinases and Bone Resorption

“…[18] Furthermore, the zinc chelator 1,10-phenanthroline or the physiological MMP inhibitors TIMP-1 and TIMP-2 reduced migration of the aggressive breast cancer cells through the bone marrow fibroblast layer. [19] We have been studying non-hydroxamic MMPIs for a long time, [20][21][22][23][24][25][26] with a particular attention towards phosphonic derivatives. [20,22,23,25] As an extension of our phosphonate program, we report herein the synthesis of new analogues containing the bisphosphonic group as a ZBG ( Figure 1) and their biological evaluation against various MMPs and against the macrophage cell line J774, a model system to screen the inhibitory effects on osteoclast activity.…”

“…The resulting oily residue was purified by flash chromatography on silica gel (eluent: CHCl 3 /iPrOH 98:2) to give the desired compound 30 as a yellowish oil (0. 21 Method C: A solution of BBr 3 (1 m, 1.85 mmol) in CH 2 Cl 2 was carefully added dropwise under N 2 atmosphere to a cooled (À30 8C) solution of the appropriate tetraalkyl bisphosphonate (19,22,23, or 27) (1.02 mmol) in anhydrous toluene (11 mL). After 6 h at 75 8C, the reaction mixture was cooled at room temperature, then CH 3 OH (5 mL) was added and stirring was continued for additional 30 min.…”

Acyclic and Cyclic Ureas (Update 2013)

“…The unprotected reagent 4-nitrophenyl N-hydroxycarbamate can be used for the direct preparation of N-hydroxyureas from amines, [350] but the two-step process is often preferable. [349,351] Similarly, primary and secondary aliphatic and aromatic amines afford N-tert-butoxyureas upon reaction with tert-butyl N-(mesitylsulfonyloxy)carbamate in dimethylformamide in the presence of a strong base (53-92%) by a Lossen-type rearrangement via tert-butoxy isocyanate. The tert-butyl group can then be cleaved under acidic conditions.…”

Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies

“…These issues prompted the search for alternative approaches to the MMP inhibition [16], such as the substitution of the ZBG with less potent, more selective zinc binders [17,18,19,20,21,22], the use of MMP-directed antibody [23] and the design of non-zinc binding inhibitors (NZIs) [24]. These ligands, commonly reported as third-generation MMPIs, have been developed for MMP-13 [25], MMP-8 [26] and MMP-12 [27] and can reach a better selectivity by missing the ZBG.…”