126926-35-0

Upstream product

• 1459-93-4 dimethyl Isophthalate 
• 1877-71-0 benzene 1,3-dicarboxylic acid monomethyl ester 
• 142-84-7 di-n-propylamine 
• 121-91-5 isophthalic acid 
• 126926-42-9 N,N-dipropyl isophthalamic acid methyl ester 

Downstream Products

• 637024-68-1 N-(2-azido-5-hydroxy-1-isobutyl-4-methyl-pentyl)-N',N'-dipropyl-isophthalamide 
• 637024-78-3 N-[(1S,2S,4R)-2-azido-1-benzyl-5-hydroxy-4-methyl-pentyl]-N',N'-dipropylisophthalamide 
• 913367-93-8 {(1S,2S)-2-(3-Dipropylcarbamoyl-benzoylamino)-1-[(3-methoxy-benzylamino)-methyl]-3-phenyl-propyl}-carbamic acid tert-butyl ester 
• 918129-66-5 {(1R,2S)-2-(3-Dipropylcarbamoyl-benzoylamino)-1-[(3-methoxy-benzylamino)-methyl]-3-phenyl-propyl}-carbamic acid benzyl ester 
• 881476-98-8 C₃₃H₅₆N₄O₅ 

Relevant academic research and scientific papers

Peptidomimetic plasmepsin inhibitors with potent anti-malarial activity and selectivity against cathepsin D

Following up the open initiative of anti-malarial drug discovery, a GlaxoSmithKline (GSK) phenotypic screening hit was developed to generate hydroxyethylamine based plasmepsin (Plm) inhibitors exhibiting growth inhibition of the malaria parasite Plasmodium falciparum at nanomolar concentrations. Lead optimization studies were performed with the aim of improving Plm inhibition selectivity versus the related human aspartic protease cathepsin D (Cat D). Optimization studies were performed using Plm IV as a readily accessible model protein, the inhibition of which correlates with anti-malarial activity. Guided by sequence alignment of Plms and Cat D, selectivity-inducing structural motifs were modified in the S3 and S4 sub-pocket occupying substituents of the hydroxyethylamine inhibitors. This resulted in potent anti-malarials with an up to 50-fold Plm IV/Cat D selectivity factor. More detailed investigation of the mechanism of action of the selected compounds revealed that they inhibit maturation of the P. falciparum subtilisin-like protease SUB1, and also inhibit parasite egress from erythrocytes. Our results indicate that the anti-malarial activity of the compounds is linked to inhibition of the SUB1 maturase plasmepsin subtype Plm X.

BACE-2 INHIBITORY COMPOUNDS AND RELATED METHODS OF USE

Provided herein are novel compounds of Formulae I-III, and methods of using the same to selectively inhibit BACE2.

Structure-based design, synthesis, X-ray studies, and biological evaluation of novel HIV-1 protease inhibitors containing isophthalamide-derived P2-ligands

We describe the design, synthesis and biological evaluation of a series of novel HIV-1 protease inhibitors bearing isophthalamide derivatives as the P2-P3 ligands. We have investigated a range of acyclic and heterocyclic amides as the extended P2-P3 ligan

Design and synthesis of potent and selective BACE-1 inhibitor

Highly potent BACE-1 protease inhibitors have been developed from an inhibitors containing a hydroxyethylene (HE) core displaying aryloxymethyl or benzyloxymethyl P1 side chain and a methoxy P1′ side chain. The target molecules were synthesized in good overall yields from chiral carbohydrate starting materials. The inhibitors show high BACE-1 potency and good, selectivity against cathepsin D, where the most potent inhibitor furnishes BACE-1 Ki ? 1 nM and displays > 1000-fold selectivity over cathepsin D.

Aspartic protease inhibitors via C1-homologation of peptidic aldehydes and studies on reduced amide isosteres

(R)-Configured isophthalic hydroxyethylamines play an important role in the inhibition of β-secretase (BACE1). We present the synthesis of a number of (S)-configured hydroxyethylamine derivatives via 2-iodoethanol intermediates and the comparison with the

BICYCLIC COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF

The present invention provides bicyclic beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer’s disease.

Norstatines from Aldehydes by sequential organocatalytic α-amination and passerini reaction

The combination of the enantioselective, organocatalytic α-amination of aldehydes by diazodicarboxylates and the Passerini reaction provides rapid access to norstatine-based peptidomimetics. These intermediates were elaborated further by deprotection and cleavage of the N-N bond to provide useful building blocks for aspartic protease inhibitors. Coupling of the compounds 76-86 with the mono-isophthalamide 91 provided moderate inhibitors of human β-secretase (BACE) 92-102. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

NOVEL ISOPHTHALATES AS BETA-SECRETASE INHIBITORS

There is provided a series of substituted isophthalates of formula (I) or a stereoisomer thereof; or a pharmaceutically acceptable salt thereof, wherein W, R3, R5 and R6 as defined herein, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein (APP) by β-secretase and, more specifically, inhibit the production of Aβ-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to β-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

CYCLIC AMINE BACE-1 INHIBITORS HAVING A BENZAMIDE SUBSTITUENT

Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R is-C(O)-N(R27)(R28) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer’s disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, and N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

BACE INHIBITORS

The present invention provides BACE inhibitors of Formula (I): methods for their use and preparation, and intermediates for their preparation.