33233-67-9Relevant articles and documents
Water soluble prodrugs of the antitumor agent 3-[(3-amino-4-methoxy)phenyl]-2-(3,4,5-trimethoxyphenyl)cyclopent-2-ene-1-one
Nam, Nguyen-Hai,Kim, Yong,You, Young-Jae,Hong, Dong-Ho,Kim, Hwan-Mook,Ahn, Byung-Zun
, p. 1021 - 1029 (2003)
Fourteen prodrugs of the antitumor agent 3-[(3-amino-4-methoxy)phenyl]-2-(3,4,5-trimethoxyphenyl)cyclopent-2-ene-1-one (1) were prepared to improve its water solubility and potency. These prodrugs include α-amino acid (1a-1h), aliphatic amino acid (1i-1l), phosphoramidate (1m), and phosphate (1n) derivatives. All of the prodrugs showed improved water solubility. A number of the amino acid prodrugs (1a, 1b, 1d-1f, 1h, 1j, and 1k) exhibited more potent antitumor activity compared to the parent compound (1). The phosphate prodrug 1n also offered a potent antitumor activity, but the phosphoramidate 1m did not show any antitumor activity in vivo. None of the prodrugs exhibited significant toxicities in mice. These results indicate that the design and preparation of the amino acid prodrugs (1a, 1b, 1d-1f, 1h, 1j, and 1k) and phosphate prodrug (1n) are beneficial for enhancing the antitumor activity of 1. The similar approaches may be used to improve water solubility and bioactivity of other poorly soluble aromatic amines.
Harnessing the anti-nociceptive potential of nk2 and nk3 ligands in the design of new multifunctional μ/δ-opioid agonist–neurokinin antagonist peptidomimetics
Ballet, Steven,Gadais, Charlène,Janecka, Anna,Martin, Charlotte,Neve, Jolien De,Piekielna-Ciesielska, Justyna
supporting information, (2021/09/13)
Opioid agonists are well-established analgesics, widely prescribed for acute but also chronic pain. However, their efficiency comes with the price of drastically impacting side effects that are inherently linked to their prolonged use. To answer these liabilities, designed multiple ligands (DMLs) offer a promising strategy by co-targeting opioid and non-opioid signaling pathways involved in nociception. Despite being intimately linked to the Substance P (SP)/neurokinin 1 (NK1) system, which is broadly examined for pain treatment, the neurokinin receptors NK2 and NK3 have so far been neglected in such DMLs. Herein, a series of newly designed opioid agonist-NK2 or-NK3 antagonists is reported. A selection of reported peptidic, pseudo-peptidic, and non-peptide neurokinin NK2 and NK3 ligands were covalently linked to the peptidic μ-opioid selective pharma-cophore Dmt-DALDA (H-Dmt-D-Arg-Phe-Lys-NH2 ) and the dual μ/δ opioid agonist H-Dmt-D-Arg-Aba-βAla-NH2 (KGOP01). Opioid binding assays unequivocally demonstrated that only hybrids SBL-OPNK-5, SBL-OPNK-7 and SBL-OPNK-9, bearing the KGOP01 scaffold, conserved nanomo-lar range μ-opioid receptor (MOR) affinity, and slightly reduced affinity for the δ-opioid receptor (DOR). Moreover, NK binding experiments proved that compounds SBL-OPNK-5, SBL-OPNK-7, and SBL-OPNK-9 exhibited (sub)nanomolar binding affinity for NK2 and NK3, opening promising opportunities for the design of next-generation opioid hybrids.
HISTONE DEMETHYLASE INHIBITORS FOR TREATING CANCERS
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Paragraph 0178-0179, (2021/01/22)
The present disclosure provides a new series of 8-hydroxyquinoline derivatives/analogs that are potent KDM4 inhibitors with high activity and selectivity against KDM4 enzymes. Also disclosed are the pharmaceutical compositions comprising such 8-hydroxyqui
CHIMERIC COMPOUNDS AND METHODS OF MANAGING NEUROLOGICAL DISORDERS OR CONDITIONS
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Page/Page column 45, (2020/09/12)
This disclosure relates to chimeric compounds and methods for managing neurological conditions. In certain embodiments, the compound comprises a chemical structure of a monoamine reuptake inhibitor conjugated to a chemical structure of a histone deacetyla