136375-70-7Relevant articles and documents
An increase in side-group hydrophobicity largely improves the potency of ritonavir-like inhibitors of CYP3A4
Samuels, Eric R.,Sevrioukova, Irina F.
, (2020/02/13)
Identification of structural determinants required for potent inhibition of drug-metabolizing cytochrome P450 3A4 (CYP3A4) could help develop safer drugs and more effective pharmacoenhancers. We utilize a rational inhibitor design to decipher structure-activity relationships in analogues of ritonavir, a highly potent CYP3A4 inhibitor marketed as pharmacoenhancer. Analysis of compounds with the R1 side-group as phenyl or naphthalene and R2 as indole or naphthalene in different stereo configuration showed that (i) analogues with the R2-naphthalene tend to bind tighter and inhibit CYP3A4 more potently than the R2-phenyl/indole containing counterparts; (ii) stereochemistry becomes a more important contributing factor, as the bulky side-groups limit the ability to optimize protein-ligand interactions; (iii) the relationship between the R1/R2 configuration and preferential binding to CYP3A4 is complex and depends on the side-group functionality/interplay and backbone spacing; and (iv) three inhibitors, 5a-b and 7d, were superior to ritonavir (IC50 of 0.055–0.085 μM vs. 0.130 μM, respectively).
Enantioselective Synthesis of 4-Substituted Dihydrocoumarins through a Zinc Bis(hydroxyamide)-Catalyzed Conjugate Addition of Terminal Alkynes
Blay, Gonzalo,Munoz, M. Carmen,Pedro, Jose R.,Sanz-Marco, Amparo
supporting information, p. 1071 - 1076 (2013/06/04)
A new enantioselective catalyst for the conjugate addition of terminal alkynes has been developed. Terminal alkynes react with 3- alkoxycarbonylcoumarins in the presence of diethylzinc and bis(hydroxyamide) ligands to give chiral non-racemic dihydrocoumarins substituted with an alkynyl group on the C-4 position with good yields and enantiomeric excesses up to 95%. Copyright
CXCR4-ANTAGONISTIC DRUGS COMPRISING NITROGEN-CONTAINING COMPOUND
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Page/Page column 100, (2010/02/05)
To provide novel nitrogen-containing compounds having antagonism to CXCR4 and remedies for disease, such as rheumatism, cancer metastasis, etc., based on the CXCR4 antagonism. Nitrogen-containing compounds represented by the following general formula and
