134703-21-2Relevant academic research and scientific papers
Diarylureas Containing 5-Membered Heterocycles as CB1 Receptor Allosteric Modulators: Design, Synthesis, and Pharmacological Evaluation
Nguyen, Thuy,Gamage, Thomas F.,Decker, Ann M.,German, Nadezhda,Langston, Tiffany L.,Farquhar, Charlotte E.,Kenakin, Terry P.,Wiley, Jenny L.,Thomas, Brian F.,Zhang, Yanan
, p. 518 - 527 (2018/10/02)
Allosteric modulators have attracted significant interest as an alternate strategy to modulate CB1 receptor signaling for therapeutic benefits that may avoid the adverse effects associated with orthosteric ligands. Here we extended our previous structure-activity relationship studies on the diarylurea-based CB1 negative allosteric modulators (NAMs) by introducing five-membered heterocycles to replace the 5-pyrrolidinylpyridinyl group in PSNCBAM-1 (1), one of the first generation CB1 allosteric modulators. Many of these compounds had comparable potency to 1 in blocking the CB1 agonist CP55,940 stimulated calcium mobilization and [35S]GTP-γ-S binding. Similar to 1, most compounds showed positive cooperativity by increasing [3H]CP55,940 binding, consistent with the positive allosteric modulator (PAM)-antagonist mechanism. Interestingly, these compounds exhibited differences in ability to increase specific binding of [3H]CP55,940 and decrease binding of the antagonist [3H]SR141716. In saturation binding studies, only increases in [3H]CP55,940 Bmax, but not Kd, were observed, suggesting that these compounds stabilize low affinity receptors into a high affinity state. Among the series, the 2-pyrrolyl analogue (13) exhibited greater potency than 1 in the [35S]GTP-γ-S binding assay and significantly enhanced the maximum binding level in the [3H]CP5,5940 binding assay, indicating greater CB1 receptor affinity and/or cooperativity.
DIARYLUREAS AS CB1 ALLOSTERIC MODULATORS
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Paragraph 70; 174, (2018/12/02)
The present invention provides novel diarylurea derivatives (compounds of formula (I)) and their uses. The compounds of the present invention are demonstrated to be allosteric modulators of the CB1 receptor, and therefore useful for the treatment of diseases and conditions mediated by CB1.
Discovery of biarylaminoquinazolines as novel tubulin polymerization inhibitors
Marzaro, Giovanni,Coluccia, Antonio,Ferrarese, Alessandro,Brun, Paola,Castagliuolo, Ignazio,Conconi, Maria Teresa,La Regina, Giuseppe,Bai, Ruoli,Silvestri, Romano,Hamel, Ernest,Chilin, Adriana
, p. 4598 - 4605 (2014/07/07)
Cell cycle experiments with our previously reported 4- biphenylaminoquinazoline (1-3) multityrosine kinase inhibitors revealed an activity profile resembling that of known tubulin polymerization inhibitors. Novel 4-biarylaminoquinazoline analogues of comp
PYRROLES FROM KETOXIMES AND ACETYLENE. 44. METHYL ARYL KETOXIMES WITH REACTIVE SUBSTITUENTS
Korostova, S. E.,Shevchenko, S. G.,Sigalov, M. V.
, p. 151 - 155 (2007/10/02)
The Trofinov reaction was extended to methyl aryl ketoximes with substituents in the benzene ring that are unstable with respect to the action of a strongly basic medium.The corresponding pyrroles and their 1-vinyl derivatives were obtained. 4-Nitroacetophenone oxime, from which only 2-phenyl- and 1-phenyl-2-phenylpyrrole were obtained, and 4-bromoacetophenone oxime, the reaction of which leads to the formation of 1-vinyl-2-(4-vinyloxyphenyl)pyrrole in addition to the principal 2-(4-bromophenyl)pyrrole, constituted exceptions.
