A Guide to Implementing Paid Family Leave - Lessons From California

Describes California's Paid Family Leave program and outlines key lessons from the legislative process and implementation in five areas: outreach and education, administration, employer issues, policy issues, and research, evaluation, and data collection

\u3cem\u3ePauley\u27s\u3c/em\u3e Legacy and Recent Trends in State Education Rights Litigation

The panel will examine the Impact of Pauley v. Kelly beyond West Virginia and its continued relevance for the current and future trajectory of education rights litigation in other states

8-substituted pyrido[3,4-<i>d</i>]pyrimidin-4(3<i>H</i>)-one derivatives as potent, cell permeable, KDM4 (JMJD2) and KDM5 (JARID1) histone lysine demethylase inhibitors

We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a series of potent JmjC histone N-methyl lysine demethylase (KDM) inhibitors which bind to Fe(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as 54j and 54k which demonstrate equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for 54k, inhibition of H3K9Me3 and H3K4Me3 demethylation in a cell-based assay.<br/

8‑Substituted Pyrido[3,4‑<i>d</i>]pyrimidin-4(3<i>H</i>)‑one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors

We report the discovery of <i>N</i>-substituted 4-(pyridin-2-yl)­thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1<i>H</i>-pyrazol-3-yl)­pyrido­[3,4-<i>d</i>]­pyrimidin-4­(3<i>H</i>)-ones, a series of potent JmjC histone <i>N</i>-methyl lysine demethylase (KDM) inhibitors which bind to Fe­(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as <b>54j</b> and <b>54k</b> which demonstrate equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for <b>54k</b>, inhibition of H3K9Me₃ and H3K4Me₃ demethylation in a cell-based assay

8‑Substituted Pyrido[3,4‑<i>d</i>]pyrimidin-4(3<i>H</i>)‑one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors

We report the discovery of <i>N</i>-substituted 4-(pyridin-2-yl)­thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1<i>H</i>-pyrazol-3-yl)­pyrido­[3,4-<i>d</i>]­pyrimidin-4­(3<i>H</i>)-ones, a series of potent JmjC histone <i>N</i>-methyl lysine demethylase (KDM) inhibitors which bind to Fe­(II) in the active site. Substitution from C4 of the pyrazole moiety allows access to the histone peptide substrate binding site; incorporation of a conformationally constrained 4-phenylpiperidine linker gives derivatives such as <b>54j</b> and <b>54k</b> which demonstrate equipotent activity versus the KDM4 (JMJD2) and KDM5 (JARID1) subfamily demethylases, selectivity over representative exemplars of the KDM2, KDM3, and KDM6 subfamilies, cellular permeability in the Caco-2 assay, and, for <b>54k</b>, inhibition of H3K9Me₃ and H3K4Me₃ demethylation in a cell-based assay