Late-stage modification of complex drug: Base-controlled Pd-catalyzed regioselective synthesis and bioactivity of arylated osimertinibs.

Achieving regioselective synthesis in complex molecules with multiple reactive sites remains a tremendous challenge in synthetic chemistry. Regiodivergent palladium-catalyzed C─H arylation of complex antitumor drug osimertinib with various aryl bromides via the late-stage functionalization strategy was demonstrated here. This reaction displayed a switch in regioselectivity under complete base control.

BL-918, a small-molecule activator of ULK1, induces cytoprotective autophagy for amyotrophic lateral sclerosis therapy.

Amyotrophic lateral sclerosis (ALS) is one of the most common fatal neurodegenerative diseases in adults. ALS pathogenesis is associated with toxic SOD1 aggregates generated by mutant SOD1. Since autophagy is responsible for the clearance of toxic protein aggregates including SOD1 aggregates, autophagy induction has been considered as a potential strategy for treating ALS.

Deep Learning Promotes the Screening of Natural Products with Potential Microtubule Inhibition Activity.

Natural microtubule inhibitors, such as paclitaxel and ixabepilone, are key sources of novel medications, which have a considerable influence on anti-tumor chemotherapy. Natural product chemists have been encouraged to create novel methodologies for screening the new generation of microtubule inhibitors from the enormous natural product library. There have been major advancements in the use of artificial intelligence in medication discovery recently.

Late-Stage Modification of Medicine: Pd-Catalyzed Direct Synthesis and Biological Evaluation of -Aryltacrine Derivatives.

A new series of -aryltacrine derivatives were designed and synthesized as cholinesterase inhibitors by the late-stage modification of tacrine, using the palladium-catalyzed Buchwald-Hartwig cross-coupling reaction. In vitro inhibition assay against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) demonstrated that most of the synthesized compounds had potent AChE inhibitory activity with negative inhibition of BuChE. Among them, -(4-(trifluoromethyl)phenyl)-tacrine () and -(4-methoxypyridin-2-yl)-tacrine () showed the most potent activity against AChE (IC values of 1.

Isolation, Structure Elucidation, Semi-Synthesis, and Structural Modification of C-Diterpenoid Alkaloids from and Their Neuroprotective Activities.

Five new aconitine-type C-diterpenoid alkaloids, apetalrines A-E (-), were isolated from . Their structures were determined by analysis of 1D and 2D NMR, IR, and HRESIMS data. Semisynthesis of apetalrine B () from its parent compound aconorine was achieved to confirm the structure proposed.

Diarylheptanoid: A privileged structure in drug discovery.

Privileged structures are widely used in the process of drug design, and provide an effective template in medicinal chemistry. Diarylheptanoids are a class of structurally distinctive compounds with a wide variety of bioactivity, raising keenly interest in the past decades. Turmeric is a golden spice from the rhizome of the plant Curcuma longa, used for food preparations and giving color since ancient times.

Five New Diterpenoids from the Seeds of Euphorbia lathyris.

A new premyrsinane-type diterpenoid, premylanin (1), and four new lathyrane-type diterpenoids named Euphorbia Factors L -L (2-5) were isolated from the seeds of Euphorbia lathyris, together with thirteen known ones (6-18). Their structures were elucidated through spectroscopic analyses, including IR, UV, HR-ESI-MS, 1D- and 2D-NMR. The cytotoxicities of compounds 1-4 and 6-18 against HCT116, MCF-7, 786-0, HepG2 cell lines were evaluated, and compound 13 exhibited considerable cytotoxic activities with an IC values of 6.

Cytotoxic Lathyrane-Type Diterpenes from Seeds of Euphorbia lathyris.

We isolated two new lathyrane-type diterpenes L (1) and L (2) along with seven known compounds (3-9) from the seeds of Euphorbia lathyris. These compounds were identified by NMR, high-resolution electrospray ionisation (HR-ESI)-MS as well as IR spectroscopy. Compounds 1 and 2 were assigned NMR spectrums with H-NMR, C-NMR, distortionless enhancement by polarization (DEPT), correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser effect spectroscopy (NOESY).