Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

102 NITRILE OXIDES
elastase release from neutrophils. In addition, one of the compounds exhibited
oral activity in a rat adjuvant arthritis test (498).
Ar
N
O
N
O N
456
N Me
Peroxisome proliferator-activated receptors (PPARs), important molecular targets
for developing drugs for the treatment of human metabolic diseases, inßammation,
and cancer, are known to be activated by a variety of structurally diverse
compounds. Using a structure-based drug design approach, a series of novel
isoxazolyl-serine-based PPAR ligands 457 [R = Boc, Cbz, o-Cl-Cbz, H,
Ph(CH2)3, CO(CH2)4Me], possessing moderate binding afÞnities to the three
PPAR subtypes, has been synthesized (499). Some of the new PPAR ligands
stimulate cardiomyocyte differentiation from murine embryonic stem (ES) cells.
Ligand 457 (R = Boc) is the most active one tested at concentrations between
1.25 to 20 μM between 2 and 6d. This is the period when mesodermal cells
become cardiomyocytes.
N
457
N O
O
O
OH
NHR
1.4.2. Nitrile Oxides in Polymer Chemistry and Technology
The ability of nitrile oxides to undergo addition and cycloaddition reactions makes
it possible to use them in polymer chemistry and technology. Major trends might
be synthesis, modiÞcation, cross-linking of polymers, addition of nucleophiles,
and 1,3-dipolar cycloaddition of nitrile oxides. Taking into account the scarcity
of reviews devoted to this topic, not only recent but also previous references will
be cited in this subsection.
1.4.2.1. Synthesis and ModiÞcation of Polymers Unstable bis(nitrile oxide),
generated by dichloroglyoxime dehydrochlorination, polymerizes in solution to
give poly(furoxan) or (in the presence of 1,3-dienes) gives rise to their being
cross-linked (500). Polymerization of terephthalonitrile dioxide and its