Latest Articles of Bioorganic & Medicinal Chemistry Letters


Design, synthesis, evaluation, and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents 10.1016/j.bmcl.2018.04.021 2018-04-11 Ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were synthesized in an attempt to develop potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by 1H NMR, 13C NMR, and HRMS. Most of the sy...
Covalent inhibitors of nicotinamide N-methyltransferase (NNMT) provide evidence for target engagement challenges in situ 10.1016/j.bmcl.2018.04.017 2018-04-10 Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide using S-adenosyl-L-methionine (SAM) as a methyl donor and, through doing so, can modulate cellular methylation potential to impact diverse epigenetic processes. NNMT has been ...
Valproic Acid Induces Three Novel Cytotoxic Secondary Metabolites in Diaporthe sp., an Endophytic Fungus from Datura inoxia Mill 10.1016/j.bmcl.2018.04.018 2018-04-10 Addition of the valproic acid (histone deacetylases inhibitor) to a culture of an endophytic fungus Diaporthe sp. harbored from Datura inoxia significantly altered its secondary metabolic profile and resulted in the isolation of three novel compounds, identif...
Agonists of the γ-Aminobutyric Acid Type B (GABAB) Receptor Derived from β-Hydroxy and β-Amino Difluoromethyl Ketones 10.1016/j.bmcl.2018.04.003 2018-04-07 Highlights • β-Hydroxy difluoromethyl ketones have distinct SAR data at the GABAB receptor. • β-Amino difluoromethyl ketones are now characterized as GABAB agonists. • Docking studies at the GABAB receptor suggest similar binding modes to baclofen.
Synthesis of 3-(3-hydroxyphenyl)pyrrolidine dopamine D3 receptor ligands with extended functionality for probing the secondary binding pocket 10.1016/j.bmcl.2018.03.084 2018-04-04 A series of 3-(3-hydroxyphenyl)pyrrolidine analogues which incorporate N-alkyl groups and N-butylamide-linked benzamide functionality have been synthesized and their in vitro binding affinities at human dopamine receptors have been evaluated. Our ligand desig...
Structure-Activity Relationship Study of a Series of Caspase Inhibitors Containing γ-Amino Acid Moiety for Treatment of Cholestatic Liver Disease 10.1016/j.bmcl.2018.04.002 2018-04-04 A series of caspase inhibitors containing γ-amino acid moiety have been synthesized. A systemic study on their structure-activity relationship of anti-apoptotic cellular activity is presented. These efforts led to the discovery of compound 20o as a potent cas...
Photoactivated 2,3-Distyrylindoles Kill Multi-Drug Resistant Bacteria 10.1016/j.bmcl.2018.04.001 2018-04-03 Compounds based on the 2,3-distyrylindole scaffold were found to exhibit bactericidal properties upon irradiation with white light. At the concentration of 1 μM, the lead compound 1 completely (ca. 109 CFU/mL) eradicated such Gram-positive organisms as S. aur...
Stereospecific synthesis of (E)-stilbene derivatives by palladium-catalyzed Suzuki-Miyaura cross-coupling reaction 10.1016/j.bmcl.2018.04.004 2018-04-03 A general procedure for the stereospecific synthesis of (E)-stilbene derivatives by palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of (E)-2-phenylethenylboronic acid pinacol ester with aryl bromides was investigated. (E)-2-phenylethenylboronic aci...
Identification and biological evaluation of thiazole-based inverse agonists of RORγt 10.1016/j.bmcl.2018.03.093 2018-04-03 The nuclear receptor retinoic acid receptor-related orphan receptor gamma t (RORγt) is a transcription factor that drives Th17 cell differentiation and IL-17 production in both innate and adaptive immune cells. The IL-23/IL-17 pathway is implicated in major a...
Discovery of Chiral Dihydropyridopyrimidinones as Potent, Selective and Orally Bioavailable Inhibitors of AKT 10.1016/j.bmcl.2018.03.092 2018-04-02 During the course of our research efforts to develop potent and selective AKT inhibitors, we discovered enatiomerically pure substituted dihydropyridopyrimidinones (DHP) as potent inhibitors of protein kinase B/AKT with excellent selectivity against ROCK2. A ...

Design, synthesis, evaluation, and molecular docking of ursolic acid derivatives containing a nitrogen heterocycle as anti-inflammatory agents

10.1016/j.bmcl.2018.04.021

2018-04-11

Ursolic acid derivatives containing oxadiazole, triazolone, and piperazine moieties were synthesized in an attempt to develop potent anti-inflammatory agents. Structures of the synthesized compounds were elucidated by 1H NMR, 13C NMR, and HRMS. Most of the sy...

Covalent inhibitors of nicotinamide N-methyltransferase (NNMT) provide evidence for target engagement challenges in situ

10.1016/j.bmcl.2018.04.017

2018-04-10

Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide using S-adenosyl-L-methionine (SAM) as a methyl donor and, through doing so, can modulate cellular methylation potential to impact diverse epigenetic processes. NNMT has been ...

Valproic Acid Induces Three Novel Cytotoxic Secondary Metabolites in Diaporthe sp., an Endophytic Fungus from Datura inoxia Mill

10.1016/j.bmcl.2018.04.018

2018-04-10

Addition of the valproic acid (histone deacetylases inhibitor) to a culture of an endophytic fungus Diaporthe sp. harbored from Datura inoxia significantly altered its secondary metabolic profile and resulted in the isolation of three novel compounds, identif...

Agonists of the γ-Aminobutyric Acid Type B (GABAB) Receptor Derived from β-Hydroxy and β-Amino Difluoromethyl Ketones

10.1016/j.bmcl.2018.04.003

2018-04-07

Highlights • β-Hydroxy difluoromethyl ketones have distinct SAR data at the GABAB receptor. • β-Amino difluoromethyl ketones are now characterized as GABAB agonists. • Docking studies at the GABAB receptor suggest similar binding modes to baclofen.

Synthesis of 3-(3-hydroxyphenyl)pyrrolidine dopamine D3 receptor ligands with extended functionality for probing the secondary binding pocket

10.1016/j.bmcl.2018.03.084

2018-04-04

A series of 3-(3-hydroxyphenyl)pyrrolidine analogues which incorporate N-alkyl groups and N-butylamide-linked benzamide functionality have been synthesized and their in vitro binding affinities at human dopamine receptors have been evaluated. Our ligand desig...

Structure-Activity Relationship Study of a Series of Caspase Inhibitors Containing γ-Amino Acid Moiety for Treatment of Cholestatic Liver Disease

10.1016/j.bmcl.2018.04.002

2018-04-04

A series of caspase inhibitors containing γ-amino acid moiety have been synthesized. A systemic study on their structure-activity relationship of anti-apoptotic cellular activity is presented. These efforts led to the discovery of compound 20o as a potent cas...

Photoactivated 2,3-Distyrylindoles Kill Multi-Drug Resistant Bacteria

10.1016/j.bmcl.2018.04.001

2018-04-03

Compounds based on the 2,3-distyrylindole scaffold were found to exhibit bactericidal properties upon irradiation with white light. At the concentration of 1 μM, the lead compound 1 completely (ca. 109 CFU/mL) eradicated such Gram-positive organisms as S. aur...

Stereospecific synthesis of (E)-stilbene derivatives by palladium-catalyzed Suzuki-Miyaura cross-coupling reaction

10.1016/j.bmcl.2018.04.004

2018-04-03

A general procedure for the stereospecific synthesis of (E)-stilbene derivatives by palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of (E)-2-phenylethenylboronic acid pinacol ester with aryl bromides was investigated. (E)-2-phenylethenylboronic aci...

Identification and biological evaluation of thiazole-based inverse agonists of RORγt

10.1016/j.bmcl.2018.03.093

2018-04-03

The nuclear receptor retinoic acid receptor-related orphan receptor gamma t (RORγt) is a transcription factor that drives Th17 cell differentiation and IL-17 production in both innate and adaptive immune cells. The IL-23/IL-17 pathway is implicated in major a...

Discovery of Chiral Dihydropyridopyrimidinones as Potent, Selective and Orally Bioavailable Inhibitors of AKT

10.1016/j.bmcl.2018.03.092

2018-04-02

During the course of our research efforts to develop potent and selective AKT inhibitors, we discovered enatiomerically pure substituted dihydropyridopyrimidinones (DHP) as potent inhibitors of protein kinase B/AKT with excellent selectivity against ROCK2. A ...