67045-01-6Relevant articles and documents
Knoevenagel condensation of unsymmetrieal malonamic esters and malonates on a solid support
Hamper, Bruce C.,Kolodziej, Stephen A.,Scates, Angela M.
, p. 2047 - 2050 (1998)
The solid phase synthesis of unsymmetrical substituted methylene malonamic acids 7 and methylene malonic ester mono acids 8 is reported. Resin-bound malonic acid 3 is obtained by treatmeat of Wang's resin with Meldrum's acid. The free carboxylic acid can be derivatized to afford either esters or amides, which readily undergo Knoevenagel condensation with aldehydes. Cleavage with TFA affords unsymmetrical β-substituted methylene malonamic acids or malonate mono acids.
Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
, p. 9067 - 9089 (2017/11/14)
Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
Amide derivatives and methods of their use
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Page/Page column 36, (2008/06/13)
Amide derivatives of the general formulae Ia and Ib: are disclosed. Pharmaceutical compositions containing these compounds, and methods for their use, inter alia, for treating and/or preventing gastrointestinal disorders, pain, and pruritus are also disclosed.
