4 research outputs found
Powerful Approach to Heterocyclic Skeletal Diversity by Sequential Three-Component Reaction of Amines, Isothiocyanates, and 1,2-Diaza-1,3-dienes
By highly efficient, one-pot, three-component reactions,
combining
one set of 1,2-diaza-1,3-dienes (DDs), primary amines, and isothiocyanates
in a different sequential order of addition, heterocyclic skeletal
diversity can be achieved. The key feature discriminating the different
heterocyclic core formation is the availability of the <i>N</i> or <i>S</i> heteronucleophile to give the first Michael
addition step affording regioselective substituted 2-thiohydantoins
or 2-iminothiazolidinones. The hydrazone or enehydrazino side chain
at the 5-position of both heterocycles represents a valuable functionality
to reach novel 5-hydroxyethylidene derivatives difficult to obtain
by other methods
Divergent Approach to Thiazolylidene Derivatives: A Perspective on the Synthesis of a Heterocyclic Skeleton from β‑Amidothioamides Reactivity
Herein we report a domino protocol
able to reach regioselectively
thiazolylidene systems by combining the reactive peculiarities of
both β-amidothioamides (ATAs) and 1,2-diaza-1,3-dienes (DDs).
Depending on the reaction conditions and/or the nature of the residue
at C4 of the heterodiene system, ATAs can act as hetero-mononucleophiles
or hetero-dinucleophiles in the diversified thiazolylidene ring assembly
Side-Chain Modified Ergosterol and Stigmasterol Derivatives as Liver X Receptor Agonists
A series of stigmasterol
and ergosterol derivatives, characterized
by the presence of oxygenated functions at C-22 and/or C-23 positions,
were designed as potential liver X receptor (LXR) agonists. The absolute
configuration of the newly created chiral centers was definitively
assigned for all the corresponding compounds. Among the 16 synthesized
compounds, <b>21</b>, <b>27</b>, and <b>28</b> were
found to be selective LXRα agonists, whereas <b>20</b>, <b>22</b>, and <b>25</b> showed good selectivity for
the LXRβ isoform. In particular, <b>25</b> showed the
same degree of potency as 22<i>R</i>-HC (<b>3</b>)
at LXRβ, while it was virtually inactive at LXRα (EC<sub>50</sub> = 14.51 μM). Interestingly, <b>13</b>, <b>19</b>, <b>20</b>, and <b>25</b> showed to be LXR
target gene-selective modulators, by strongly inducing the expression
of <i>ABCA1</i>, while poorly or not activating the lipogenic
genes <i>SREBP1</i> and <i>SCD1</i> or <i>FASN</i>, respectively
Novel Analgesic/Anti-Inflammatory Agents: 1,5-Diarylpyrrole Nitrooxyalkyl Ethers and Related Compounds as Cyclooxygenase‑2 Inhibiting Nitric Oxide Donors
A series of 3-substituted 1,5-diarylpyrroles
bearing a nitrooxyalkyl
side chain linked to different spacers were designed. New classes
of pyrrole-derived nitrooxyalkyl inverse esters, carbonates, and ethers
(<b>7</b>–<b>10</b>) as COX-2 selective inhibitors
and NO donors were synthesized and are herein reported. By taking
into account the metabolic conversion of nitrooxyalkyl ethers (<b>9</b>, <b>10</b>) into corresponding alcohols, derivatives <b>17</b> and <b>18</b> were also studied. Nitrooxy derivatives
showed NO-dependent vasorelaxing properties, while most of the compounds
proved to be very potent and selective COX-2 inhibitors in in vitro
experimental models. Further in vivo studies on compounds <b>9a</b>,<b>c</b> and <b>17a</b> highlighted good anti-inflammatory
and antinociceptive activities. Compound <b>9c</b> was able
to inhibit glycosaminoglycan (GAG) release induced by interleukin-1β
(IL-1β), showing cartilage protective properties. Finally, molecular
modeling and <sup>1</sup>H- and <sup>13</sup>C-NMR studies performed
on compounds <b>6c</b>,<b>d</b>, <b>9c</b>, and <b>10b</b> allowed the right conformation of nitrooxyalkyl ester
and ether side chain of these molecules within the COX-2 active site
to be assessed