856875-46-2

Upstream product

• 536-74-3 phenylacetylene 
• 40396-54-1 1-(3-bromophenyl)-2-phenylethane-1,2-dione 
• 22661-87-6 1-methylguanidine hydrochloride 
• 3132-99-8 m-bromobenzoic aldehyde 
• 1392015-27-8 (Z)-1-(3-bromophenyl)-2-phenyl-2-(phenylimino)ethan-1-one 

Downstream Products

• 1083179-43-4 2-amino-5-(3'-{[dimethyl(oxido)-λ4-sulfanylidene]amino}-5'-methoxybiphenyl-3-yl)-3-methyl-5-phenyl-3,5-dihydro-4H-imidazol-4-one hydrochloride 
• 887911-80-0 C₂₁H₁₇FN₄O 
• 887911-87-7 C₂₁H₁₇ClN₄O 
• 887911-21-9 (R)-2-imino-5-(3'-methoxy-[1,1'-biphenyl]-3-yl)-3-methyl-5-phenyl-imidazolidin-4-one 
• 856885-13-7 C₂₃H₂₁N₃O₂ 
• 856885-29-5 C₂₄H₂₃N₃O₂ 
• 1049655-77-7 C₂₁H₁₈N₄O 
• 856875-79-1 2-imino-3-methyl-5-phenyl-5-[3-(pyridin-3-yl)phenyl]imidazolidin-4-one 
• 856875-78-0 C₂₁H₁₈N₄O 
• 887911-20-8 C₂₂H₁₇N₅O 
• 856875-77-9 C₂₂H₁₉N₃O 
• 1370656-78-2 C₂₀H₁₇N₅O 
• 887911-14-0 C₂₂H₂₀N₄O 
• 1370656-79-3 C₂₃H₂₁N₃O₂ 

Relevant academic research and scientific papers

Design, synthesis and evaluation of 2-amino-imidazol-4-one derivatives as potent β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) inhibitors

Inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) to prevent brain β-amyloid (Aβ) peptide's formation is a potential effective approach to treat Alzheimer's disease. In this report we described a structure-based optimization of a series of BACE1 inhibitors derived from an iminopyrimidinone scaffold W-41 (IC50 = 7.1 μM) by Wyeth, which had good selectivity and brain permeability but low activity. The results showed that occupying the S3 cavity of BACE1 enzyme could be an effective strategy to increase the biological activity, and five compounds exhibited stronger inhibitory activity and higher liposolubility than W-41, with L-5 was the most potent inhibitor against BACE1 (IC50 = 0.12 μM, logP = 2.49).

Discovery of an orally available, brain penetrant BACE1 inhibitor that affords robust CNS Aβ reduction

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 physicochemical properties culminated in the discovery of compound 16, which potently reduced cortex and CSF Aβ40 levels when administered orally to rats.

Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor

From an initial lead 1, a structure-based design approach led to identification of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers CNS-derived Aβ following oral administration to rats. Herein we report 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 the optimized compound.

NEW COMPOUNDS 835

This invention relates to novel compounds having the structural formula I below: and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Di

NEW COMPOUNDS

This invention relates to novel compounds having the structural formula I below: and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

NOVEL 2-AMINO-IMIDAZOLE-4-ONE COMPOUNDS AND THEIR USE IN THE MANUFACTURE OF A MEDICAMENT TO BE USED IN THE TREATMENT OF COGNITIVE IMPAIRMENT, ALZHEIMER’S DISEASE, NEURODEGENERATION AND DEMENTIA

This invention relates to novel compounds having the structural formula I below and to their pharmaceutically acceptable salts, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Di