Category: 917471-30-8

Ashworth, Ian W. published the artcileProcess Development of a Suzuki Reaction Used in the Manufacture of Lanabecestat, HPLC of Formula: 917471-30-8, the main research area is lanabecestat preparation; Suzuki coupling diethanolamine alkynylpyridinylboronate bromodispirocyclohexaneindaneimidazole key step; hydrolysis kinetics diethanolamine alkynylpyridinylboronate; effect diethanolamine removal palladium lanabecestat.

A process for preparation of the potential anti-Alzheimer’s agent lanabecestat was developed by coupling of an alkynylpyridinylboronic acid diethanolamine ester with a bromodispirocyclohexaneindaneimidazole in the presence of Pd(AmPhos)2Cl2 and K3PO4 in EtOH/H2O; the new process reduced the need for solvent changes and difficult isolation steps and decreased the amount of palladium detected in the final product without the use of solid-phase extractants. The kinetics of hydrolysis of the diethanolamine boronate and the free boronic acid was determined; diethanolamine generated in the hydrolysis decreased the rate of coupling but likely improved the purge of palladium from the product.

Organic Process Research & Development published new progress about Hydrolysis. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, HPLC of Formula: 917471-30-8.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ashworth, Ian W. published the artcileProcess Development of a Suzuki Reaction Used in the Manufacture of Lanabecestat, HPLC of Formula: 917471-30-8, the main research area is lanabecestat preparation; Suzuki coupling diethanolamine alkynylpyridinylboronate bromodispirocyclohexaneindaneimidazole key step; hydrolysis kinetics diethanolamine alkynylpyridinylboronate; effect diethanolamine removal palladium lanabecestat.

A process for preparation of the potential anti-Alzheimer’s agent lanabecestat was developed by coupling of an alkynylpyridinylboronic acid diethanolamine ester with a bromodispirocyclohexaneindaneimidazole in the presence of Pd(AmPhos)2Cl2 and K3PO4 in EtOH/H2O; the new process reduced the need for solvent changes and difficult isolation steps and decreased the amount of palladium detected in the final product without the use of solid-phase extractants. The kinetics of hydrolysis of the diethanolamine boronate and the free boronic acid was determined; diethanolamine generated in the hydrolysis decreased the rate of coupling but likely improved the purge of palladium from the product.

Organic Process Research & Development published new progress about Hydrolysis. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, HPLC of Formula: 917471-30-8.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ren, Hang published the artcileVersatile synthesis and biological evaluation of novel 3′-fluorinated purine nucleosides, Category: pyridine-derivatives, the main research area is Suzuki Stille coupling nucleoside fluororibose human aminopurine preparation antitumor; 3’-fluororibonucleoside; 6-substituted purine; anticancer; purine nucleoside; synthesis.

A unified synthetic strategy accessing novel 3′-fluorinated purine nucleoside derivatives and their biol. evaluation were achieved. Novel 3′-fluorinated analogs were constructed from a common 3′-deoxy-3′-fluororibofuranose intermediate. Employing Suzuki and Stille cross-coupling reactions, fifteen 3′-fluororibose purine nucleosides, e.g. I, and eight 3′-fluororibose 2-chloro/2-aminopurine nucleosidese, e.g. II, with various substituents at position 6 of the purine ring were efficiently synthesized. Furthermore, 3′-fluorine analogs of natural products nebularine and 6-methylpurine riboside were constructed via our convergent synthetic strategy. Synthesized nucleosides were tested against HT116 (colon cancer) and 143B (osteosarcoma cancer) tumor cell lines. We have demonstrated 3′-fluorine purine nucleoside analogs display potent tumor cell growth inhibition activity at sub- or low micromolar concentration

Beilstein Journal of Organic Chemistry published new progress about Antitumor agents. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Mandal, Mihirbaran published the artcileDesign and Validation of Bicyclic Iminopyrimidinones As Beta Amyloid Cleaving Enzyme-1 (BACE1) Inhibitors: Conformational Constraint to Favor a Bioactive Conformation, Synthetic Route of 917471-30-8, the main research area is bicyclic iminopyrimidinone preparation BACE1 inhibitor amyloid Alzheimer’s.

On the basis of our observation that the biaryl substituent of iminopyrimidinone 7 must be in a pseudoaxial conformation to occupy the contiguous S1-S3 subsites of BACE1, we have designed a novel fused bicyclic iminopyrimidinone scaffold intended to favor this bioactive conformation. Strategic incorporation of a nitrogen atom in the new constrained ring allowed us to develop SAR around the S2′ binding pocket and ultimately resulted in analogs with low nanomolar potency for BACE1. In particular, optimization of the prime side substituent led to major improvements in potency by displacement of two conserved water mols. from a region near S2′. Further optimization of the pharmacokinetic properties of this fused pyrrolidine series, in conjunction with facile access to a rat pharmacodynamic model, led to identification of compound 43, which is an orally active, brain penetrant inhibitor that reduces Aβ40 in the plasma, CSF, and cortex of rats in a dose-dependent manner.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Synthetic Route of 917471-30-8.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Cumming, Jared N. published the artcileStructure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor, Quality Control of 917471-30-8, the main research area is iminohydantoin imidazolidinone propynylpyridinylphenyl preparation BACE1 inhibitor Alzheimers.

From an initial lead 2-imino-1-methyl-4,4-diphenyl-5-imidazolidinone, a structure-based design approach led to identification of the novel, high-affinity iminohydantoin BACE1 inhibitor I that lowers CNS-derived Aβ following oral administration to rats. SAR development in the S3 and F’ subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for I are reported.

Bioorganic & Medicinal Chemistry Letters published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Quality Control of 917471-30-8.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Scott, Jack D. published the artcileDiscovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer’s Disease, Formula: C8H8BNO2, the main research area is verubecestat preparation BACE1 inhibitor structure activity Alzheimer disease.

Verubecestat (MK-8931), a diaryl amide substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clin. evaluation for the treatment of mild to moderate and prodromal Alzheimer’s disease. Although not selective over the closely related aspartyl protease BACE2, verubecesat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain Aβ levels in rats and nonhuman primates, and CSF Aβ levels in humans. In this annotation, the authors describe the discovery of verubecesat, including design, validation, and selected SAR around the novel iminothiadiazinane dioxide core, as well as aspects of its preclin. and Phase 1 clin. characterization.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Formula: C8H8BNO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Gravenfors, Ylva published the artcileNew Aminoimidazoles as β-Secretase (BACE-1) Inhibitors Showing Amyloid-β (Aβ) Lowering in Brain, Application of (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, the main research area is aminoimidazole BACE1 inhibitor preparation crystal structure SAR permeability hERG; amyloid beta reduction brain aminoimidazole BACE1 inhibitor.

Amino-2H-imidazoles are described as a new class of BACE-1 inhibitors for the treatment of Alzheimer’s disease. Synthetic methods, crystal structures, and structure-activity relationships for target activity, permeability, and hERG activity are reported and discussed. Compound (S)-1m (I) was one of the most promising compounds in this report, with high potency in the cellular assay and a good overall profile. When guinea pigs were treated with compound (S)-1m, a concentration and time dependent decrease in Aβ40 and Aβ42 levels in plasma, brain, and CSF was observed The maximum reduction of brain Aβ was 40-50%, 1.5 h after oral dosing (100 μmol/kg). The results presented highlight the potential of this new class of BACE-1 inhibitors with good target potency and with low effect on hERG, in combination with a fair CNS exposure in vivo.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Application of (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Stamford, Andrew W. published the artcileDiscovery of an Orally Available, Brain Penetrant BACE1 Inhibitor That Affords Robust CNS Aβ Reduction, Safety of (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, the main research area is preparation oral brain penetrant BACE1 amyloid inhibitor Alzheimer’s; Alzheimer’s disease; Aβ40; BACE1; X-ray crystallography; iminopyrimidinone; inhibitor.

Inhibition of BACE1 to prevent brain Aβ peptide formation is a potential disease-modifying approach to the treatment of Alzheimer’s disease. Despite over a decade of drug discovery efforts, the identification of brain-penetrant BACE1 inhibitors that substantially lower CNS Aβ levels following systemic administration remains challenging. In this report we describe structure-based optimization of a series of brain-penetrant BACE1 inhibitors derived from an iminopyrimidinone scaffold. Application of structure-based design in tandem with control of physicochem. properties culminated in the discovery of compound 16, which potently reduced cortex and CSF Aβ40 levels when administered orally to rats.

ACS Medicinal Chemistry Letters published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Safety of (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ciordia, Myriam published the artcileApplication of Free Energy Perturbation for the Design of BACE1 Inhibitors, Product Details of C8H8BNO2, the main research area is free energy perturbation calculation BACE1 inhibitor drug design Alzheimer.

Novel spiroaminodihydropyrroles probing for optimized interactions at the P3 pocket of β-secretase 1 (BACE1) were designed with the use of free energy perturbation (FEP) calculations The resulting mols. showed pIC50 potencies in enzymic BACE1 inhibition assays ranging from approx. 5 to 7. Good correlation was observed between the predicted activity from the FEP calculations and exptl. activity. Simulations run with a default 5 ns approach delivered a mean unsigned error (MUE) between prediction and experiment of 0.58 and 0.91 kcal/mol for retrospective and prospective applications, resp. With longer simulations of 10 and 20 ns, the MUE was in both cases 0.57 kcal/mol for the retrospective application, and 0.69 and 0.59 kcal/mol for the prospective application. Other considerations that impact the quality of the calculations are discussed. This work provides an example of the value of FEP as a computational tool for drug discovery.

Journal of Chemical Information and Modeling published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Product Details of C8H8BNO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wang, Dongping published the artcileDimeric Manganese-Catalyzed Hydroarylation and Hydroalkenylation of Unsaturated Amides, COA of Formula: C8H8BNO2, the main research area is aralkyl alkenyl amide regioselective chemoselective preparation; gamma delta lactam regioselective preparation; dimanganese catalyst regioselective chemoselective arylation alkenylation unsaturated amide; regioselective chlorocyclization phenylsulfenocyclization unsaturated amide; alkene; alkenylation; arylation; homogeneous catalysis; manganese.

In the presence of the manganese(I) dimer Mn2Br2(CO)8, either K2CO3 or CsF, and ethanol, α,β-unsaturated amides underwent chemo- and regioselective arylation and alkenylation reactions with aryl- and alkenylboronic acids to yield β-aryl amides and γ,δ-unsaturated amides. Selected γ,δ-unsaturated amides underwent chlorocyclization and phenylsulfenocyclization reactions to yield γ- and δ-lactams.

Angewandte Chemie, International Edition published new progress about Amides Role: SPN (Synthetic Preparation), PREP (Preparation) (β-aryl). 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, COA of Formula: C8H8BNO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem